Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, hematology-oncology fellows, surgeons and other healthcare providers involved in the treatment of gastrointestinal (GI) cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and clinical relevance of human epidermal growth factor receptor 2 (HER2) amplification or overexpression in various GI cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate published clinical trial findings with HER2-directed therapies for HER2-positive biliary tract cancers, and optimally incorporate available agents into the clinical care of appropriately selected patients.
• Review published and emerging research findings with HER2-targeted therapies for patients with HER2-positive gastroesophageal cancers, and assess the current and future role of various agents and regimens.
• Recall available data with HER2-targeted agents and strategies for patients with previously treated HER2-overexpressing colorectal cancer, and optimally identify candidates who may be appropriate for these approaches.
• Appraise the side effects associated with HER2-directed therapies with established efficacy in GI cancers, and use this information to develop supportive management plans for patients.
• Recall the design of ongoing clinical trials evaluating novel HER2-directed strategies for HER2-positive GI cancers, and counsel appropriately selected patients about availability and participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Proceedings: Research To Practice designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 1.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/ASCOGI26/HER2PosGI/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Haley Ellis, MD
Medical Oncologist
Massachusetts General Hospital
Instructor of Medicine
Harvard Medical School
Boston, Massachusetts

Advisory Committees: AstraZeneca Pharmaceuticals LP, Cogent Biosciences, Jazz Pharmaceuticals Inc; Honoraria: Incyte Corporation, Jazz Pharmaceuticals Inc; Nonrelevant Financial Relationships: Medscape, OncLive, The Jackson Laboratory.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Consulting Agreements: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia, Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Fosun Pharma, Galapagos NV, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, iTeos Therapeutics, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck KGaA, Microbial Machines, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Novocure Inc, Pfizer Inc, Pierre Fabre, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Trishula Therapeutics, Zymeworks Inc.

Zev Wainberg, MD, MSc
Co-Director, GI Oncology Program
Director of Early Phase Clinical Research
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, EMD Serono Inc, Gilead Sciences Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Novartis, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Arcus Biosciences, Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Pfizer Inc.

MODERATOR
Lionel A Kankeu Fonkoua, MD
Senior Associate Consultant
Assistant Professor of Oncology Division of Medical Oncology, GI Cancer Program
Mayo Clinic
Rochester, Minnesota

No relevant conflicts of interest to disclose.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: January 2026
Expiration date: January 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Ellis

Ayasun R et al. The role of HER2 status in the biliary tract cancers. Cancers (Basel) 2023;15(9):2628. Abstract

Bartley AN et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35(4):446-44. Abstract

Harding JJ et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): Post hoc analysis of the HERIZON-BTC-01 trial. Gastrointestinal Cancers Symposium 2026;Abstract 545.

Harding JJ et al. HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). Gastrointestinal Cancers Symposium 2025;Abstract TPS648.

Ikeda M et al. Randomized, open-label, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01. ESMO 2024;Abstract 261TiP.

Inoue K et al. Clinicomolecular profile and efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2-amplified advanced biliary tract cancer. JCO Precis Oncol 2025:e2400718. Abstract

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10):103706. Abstract

Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22(5):690-701. Abstract

Lee C et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Gastrointestinal Cancers Symposium 2025;Abstract 629.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Oh D-Y et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol 2025;83(5):1092-101. Abstract

Ohba A et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol 2024;42(27):3207-17. Abstract

Pant S et al. Zanidatamab in HER2-positive metastatic biliary tract cancer: Final results from HERIZON-BTC-01. JAMA Oncol 2025;12(1):106-9. Abstract

Søreide K et al. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. Abstract

Dr Wainberg

Cammarota A et al. Targeting HER2 in gastroesophageal cancer: A new appetite for an old plight. Drugs 2025;85(3):361-83. Abstract

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancer Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Janjigian YY et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. ESMO 2024;Abstract 1400O.

Janjigian YY et al. Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). ESMO 2024;Abstract 1401O.

Jubashi A et al. Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer. Gastric Cancer 2025;28(1):63-73. Abstract

Klempner et al. ERBB2 copy number (CN) as a quantitative biomarker for real-world (RW) outcomes to anti-HER2 therapy in advanced gastroesophageal adenocarcinoma (adv GEA). ASCO 2021;Abstract 4045.

Shitara K et al. An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy (chemo) ± pembrolizumab (pembro) versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction (GEJ) cancer: DESTINY-Gastric05. ASCO 2025;Abstract TPS4207.

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Shitara K et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: Exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J Clin Oncol 2023;41(4):816-25. Abstract

Yang H et al. Oesophageal cancer. Lancet 2024;404(10466):1991-2005. Abstract

Prof Van Cutsem

Germani MM et al. Impact of human epidermal growth factor receptor 2 in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab or anti-EGFRs: Exploratory analysis of eight randomized trials. J Clin Oncol 2025;43(29):3184-97. Abstract

Meric-Bernstam F et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: A phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23(12):1558-70. Abstract

Oh D-Y, Bang Y-J. HER2-targeted therapies – A role beyond breast cancer. Nat Rev Clin Oncol 2020;17(1):33-48. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2025;21(3):303-11. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Vaghi C et al. Targeting HER2 in metastatic colorectal cancer: Current therapies, biomarker refinement, and emerging strategies. Drugs 2026;86(1):37-57. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of gastrointestinal cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and clinical relevance of human epidermal growth factor receptor 2 (HER2) amplification or overexpression in various GI cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate published clinical trial findings with HER2-directed therapies for HER2-positive biliary tract cancers, and optimally incorporate available agents into the clinical care of appropriately selected patients.
• Appraise the side effects associated with HER2-directed therapies with established efficacy in GI cancers, and use this information to develop supportive management plans for patients.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Proceedings: Research To Practice designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 0.5 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
To receive credit for an activity in this series, the participant should review the CME information, listen to or view the MP3s, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Program: ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/1/Video and evaluation ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/1/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Haley Ellis, MD
Medical Oncologist
Massachusetts General Hospital
Instructor of Medicine
Harvard Medical School
Boston, Massachusetts

Advisory Committees: AstraZeneca Pharmaceuticals LP, Cogent Biosciences, Jazz Pharmaceuticals Inc; Honoraria: Incyte Corporation, Jazz Pharmaceuticals Inc; Nonrelevant Financial Relationships: Medscape, OncLive, The Jackson Laboratory.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Consulting Agreements: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia, Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Fosun Pharma, Galapagos NV, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, iTeos Therapeutics, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck KGaA, Microbial Machines, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Novocure Inc, Pfizer Inc, Pierre Fabre, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Trishula Therapeutics, Zymeworks Inc.

Zev Wainberg, MD, MSc
Co-Director, GI Oncology Program
Director of Early Phase Clinical Research
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, EMD Serono Inc, Gilead Sciences Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Novartis, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Arcus Biosciences, Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Pfizer Inc.

MODERATOR
Lionel A Kankeu Fonkoua, MD
Senior Associate Consultant
Assistant Professor of Oncology Division of Medical Oncology, GI Cancer Program
Mayo Clinic
Rochester, Minnesota

No relevant financial relationships to disclose.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: March 2026
Expiration date: March 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Ellis

Ayasun R et al. The role of HER2 status in the biliary tract cancers. Cancers (Basel) 2023;15(9):2628. Abstract

Bartley AN et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35(4):446-44. Abstract

Harding JJ et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): Post hoc analysis of the HERIZON-BTC-01 trial. Gastrointestinal Cancers Symposium 2026;Abstract 545.

Harding JJ et al. HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). Gastrointestinal Cancers Symposium 2025;Abstract TPS648.

Ikeda M et al. Randomized, open-label, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01. ESMO 2024;Abstract 261TiP.

Inoue K et al. Clinicomolecular profile and efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2-amplified advanced biliary tract cancer. JCO Precis Oncol 2025:e2400718. Abstract

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10):103706. Abstract

Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22(5):690-701. Abstract

Lee C et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Gastrointestinal Cancers Symposium 2025;Abstract 629.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Oh D-Y et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol 2025;83(5):1092-101. Abstract

Ohba A et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol 2024;42(27):3207-17. Abstract

Pant S et al. Zanidatamab in HER2-positive metastatic biliary tract cancer: Final results from HERIZON-BTC-01. JAMA Oncol 2025;12(1):106-9. Abstract

Søreide K et al. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. Abstract

Dr Wainberg

Cammarota A et al. Targeting HER2 in gastroesophageal cancer: A new appetite for an old plight. Drugs 2025;85(3):361-83. Abstract

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancer Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Janjigian YY et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. ESMO 2024;Abstract 1400O.

Janjigian YY et al. Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). ESMO 2024;Abstract 1401O.

Jubashi A et al. Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer. Gastric Cancer 2025;28(1):63-73. Abstract

Klempner et al. ERBB2 copy number (CN) as a quantitative biomarker for real-world (RW) outcomes to anti-HER2 therapy in advanced gastroesophageal adenocarcinoma (adv GEA). ASCO 2021;Abstract 4045.

Shitara K et al. An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy (chemo) ± pembrolizumab (pembro) versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction (GEJ) cancer: DESTINY-Gastric05. ASCO 2025;Abstract TPS4207.

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Shitara K et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: Exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J Clin Oncol 2023;41(4):816-25. Abstract

Yang H et al. Oesophageal cancer. Lancet 2024;404(10466):1991-2005. Abstract

Prof Van Cutsem

Germani MM et al. Impact of human epidermal growth factor receptor 2 in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab or anti-EGFRs: Exploratory analysis of eight randomized trials. J Clin Oncol 2025;43(29):3184-97. Abstract

Meric-Bernstam F et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: A phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23(12):1558-70. Abstract

Oh D-Y, Bang Y-J. HER2-targeted therapies – A role beyond breast cancer. Nat Rev Clin Oncol 2020;17(1):33-48. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2025;21(3):303-11. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Vaghi C et al. Targeting HER2 in metastatic colorectal cancer: Current therapies, biomarker refinement, and emerging strategies. Drugs 2026;86(1):37-57. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of gastrointestinal cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and clinical relevance of human epidermal growth factor receptor 2 (HER2) amplification or overexpression in various GI cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate published clinical trial findings with HER2-directed therapies for HER2-positive biliary tract cancers, and optimally incorporate available agents into the clinical care of appropriately selected patients.
• Appraise the side effects associated with HER2-directed therapies with established efficacy in GI cancers, and use this information to develop supportive management plans for patients.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Proceedings: Research To Practice designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 0.5 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
To receive credit for an activity in this series, the participant should review the CME information, listen to or view the MP3s, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Program: ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/2/Video and evaluation ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/2/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Haley Ellis, MD
Medical Oncologist 
Mass General Brigham Cancer Institute 
Harvard Medical School 
Boston, Massachusetts 

Advisory Committees: AstraZeneca Pharmaceuticals LP, Cogent Biosciences, Jazz Pharmaceuticals Inc; Honoraria: Incyte Corporation, Jazz Pharmaceuticals Inc; Nonrelevant Financial Relationships: Medscape, OncLive, The Jackson Laboratory.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Consulting Agreements: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia, Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Fosun Pharma, Galapagos NV, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, iTeos Therapeutics, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck KGaA, Microbial Machines, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Novocure Inc, Pfizer Inc, Pierre Fabre, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Trishula Therapeutics, Zymeworks Inc.

Zev Wainberg, MD, MSc
Co-Director, GI Oncology Program
Director of Early Phase Clinical Research
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, EMD Serono Inc, Gilead Sciences Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Novartis, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Arcus Biosciences, Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Pfizer Inc.

MODERATOR
Lionel A Kankeu Fonkoua, MD
Senior Associate Consultant
Assistant Professor of Oncology
Division of Medical Oncology, GI Cancer Program
Mayo Clinic
Rochester, Minnesota

No relevant financial relationships to disclose.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: March 2026
Expiration date: March 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Ellis

Ayasun R et al. The role of HER2 status in the biliary tract cancers. Cancers (Basel) 2023;15(9):2628. Abstract

Bartley AN et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35(4):446-44. Abstract

Harding JJ et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): Post hoc analysis of the HERIZON-BTC-01 trial. Gastrointestinal Cancers Symposium 2026;Abstract 545.

Harding JJ et al. HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). Gastrointestinal Cancers Symposium 2025;Abstract TPS648.

Ikeda M et al. Randomized, open-label, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01. ESMO 2024;Abstract 261TiP.

Inoue K et al. Clinicomolecular profile and efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2-amplified advanced biliary tract cancer. JCO Precis Oncol 2025:e2400718. Abstract

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10):103706. Abstract

Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22(5):690-701. Abstract

Lee C et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Gastrointestinal Cancers Symposium 2025;Abstract 629.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Oh D-Y et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol 2025;83(5):1092-101. Abstract

Ohba A et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol 2024;42(27):3207-17. Abstract

Pant S et al. Zanidatamab in HER2-positive metastatic biliary tract cancer: Final results from HERIZON-BTC-01. JAMA Oncol 2025;12(1):106-9. Abstract

Søreide K et al. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. Abstract

Dr Wainberg

Cammarota A et al. Targeting HER2 in gastroesophageal cancer: A new appetite for an old plight. Drugs 2025;85(3):361-83. Abstract

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancer Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Janjigian YY et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. ESMO 2024;Abstract 1400O.

Janjigian YY et al. Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). ESMO 2024;Abstract 1401O.

Jubashi A et al. Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer. Gastric Cancer 2025;28(1):63-73. Abstract

Klempner et al. ERBB2 copy number (CN) as a quantitative biomarker for real-world (RW) outcomes to anti-HER2 therapy in advanced gastroesophageal adenocarcinoma (adv GEA). ASCO 2021;Abstract 4045.

Shitara K et al. An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy (chemo) ± pembrolizumab (pembro) versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction (GEJ) cancer: DESTINY-Gastric05. ASCO 2025;Abstract TPS4207.

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Shitara K et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: Exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J Clin Oncol 2023;41(4):816-25. Abstract

Yang H et al. Oesophageal cancer. Lancet 2024;404(10466):1991-2005. Abstract

Prof Van Cutsem

Germani MM et al. Impact of human epidermal growth factor receptor 2 in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab or anti-EGFRs: Exploratory analysis of eight randomized trials. J Clin Oncol 2025;43(29):3184-97. Abstract

Meric-Bernstam F et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: A phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23(12):1558-70. Abstract

Oh D-Y, Bang Y-J. HER2-targeted therapies – A role beyond breast cancer. Nat Rev Clin Oncol 2020;17(1):33-48. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2025;21(3):303-11. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Vaghi C et al. Targeting HER2 in metastatic colorectal cancer: Current therapies, biomarker refinement, and emerging strategies. Drugs 2026;86(1):37-57. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of gastrointestinal cancers.

LEARNING OBJECTIVES

• Review published and emerging research findings with human epidermal growth factor receptor 2 (HER2)-targeted therapies for patients with HER2-positive or HER2-low gastroesophageal cancers, and assess their current and future roles in treatment.
• Appreciate the clinical relevance of HER2 amplification or mutation for colorectal cancer, and consider the implications for biomarker assessment and clinical management.
• Evaluate published clinical trial findings with HER2-directed therapies for HER2-positive metastatic colorectal cancer, and optimally incorporate available agents into the clinical care of appropriately selected patients.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Proceedings: Research To Practice designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 0.5 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
To receive credit for an activity in this series, the participant should review the CME information, listen to or view the MP3s, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Program: ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/3/Video and evaluation ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/3/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Haley Ellis, MD
Medical Oncologist 
Mass General Brigham Cancer Institute 
Harvard Medical School 
Boston, Massachusetts 

Advisory Committees: AstraZeneca Pharmaceuticals LP, Cogent Biosciences, Jazz Pharmaceuticals Inc; Honoraria: Incyte Corporation, Jazz Pharmaceuticals Inc; Nonrelevant Financial Relationships: Medscape, OncLive, The Jackson Laboratory.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Consulting Agreements: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia, Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Fosun Pharma, Galapagos NV, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, iTeos Therapeutics, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck KGaA, Microbial Machines, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Novocure Inc, Pfizer Inc, Pierre Fabre, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Trishula Therapeutics, Zymeworks Inc.

Zev Wainberg, MD, MSc
Co-Director, GI Oncology Program
Director of Early Phase Clinical Research
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, EMD Serono Inc, Gilead Sciences Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Novartis, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Arcus Biosciences, Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Pfizer Inc.

MODERATOR
Lionel A Kankeu Fonkoua, MD
Senior Associate Consultant
Assistant Professor of Oncology
Division of Medical Oncology, GI Cancer Program
Mayo Clinic
Rochester, Minnesota

No relevant financial relationships to disclose.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: April 2026
Expiration date: April 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Ellis

Ayasun R et al. The role of HER2 status in the biliary tract cancers. Cancers (Basel) 2023;15(9):2628. Abstract

Bartley AN et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35(4):446-44. Abstract

Harding JJ et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): Post hoc analysis of the HERIZON-BTC-01 trial. Gastrointestinal Cancers Symposium 2026;Abstract 545.

Harding JJ et al. HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). Gastrointestinal Cancers Symposium 2025;Abstract TPS648.

Ikeda M et al. Randomized, open-label, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01. ESMO 2024;Abstract 261TiP.

Inoue K et al. Clinicomolecular profile and efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2-amplified advanced biliary tract cancer. JCO Precis Oncol 2025:e2400718. Abstract

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10):103706. Abstract

Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22(5):690-701. Abstract

Lee C et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Gastrointestinal Cancers Symposium 2025;Abstract 629.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Oh D-Y et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol 2025;83(5):1092-101. Abstract

Ohba A et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol 2024;42(27):3207-17. Abstract

Pant S et al. Zanidatamab in HER2-positive metastatic biliary tract cancer: Final results from HERIZON-BTC-01. JAMA Oncol 2025;12(1):106-9. Abstract

Søreide K et al. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. Abstract

Dr Wainberg

Cammarota A et al. Targeting HER2 in gastroesophageal cancer: A new appetite for an old plight. Drugs 2025;85(3):361-83. Abstract

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancer Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Janjigian YY et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. ESMO 2024;Abstract 1400O.

Janjigian YY et al. Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). ESMO 2024;Abstract 1401O.

Jubashi A et al. Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer. Gastric Cancer 2025;28(1):63-73. Abstract

Klempner et al. ERBB2 copy number (CN) as a quantitative biomarker for real-world (RW) outcomes to anti-HER2 therapy in advanced gastroesophageal adenocarcinoma (adv GEA). ASCO 2021;Abstract 4045.

Shitara K et al. An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy (chemo) ± pembrolizumab (pembro) versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction (GEJ) cancer: DESTINY-Gastric05. ASCO 2025;Abstract TPS4207.

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Shitara K et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: Exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J Clin Oncol 2023;41(4):816-25. Abstract

Yang H et al. Oesophageal cancer. Lancet 2024;404(10466):1991-2005. Abstract

Prof Van Cutsem

Germani MM et al. Impact of human epidermal growth factor receptor 2 in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab or anti-EGFRs: Exploratory analysis of eight randomized trials. J Clin Oncol 2025;43(29):3184-97. Abstract

Meric-Bernstam F et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: A phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23(12):1558-70. Abstract

Oh D-Y, Bang Y-J. HER2-targeted therapies – A role beyond breast cancer. Nat Rev Clin Oncol 2020;17(1):33-48. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2025;21(3):303-11. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Vaghi C et al. Targeting HER2 in metastatic colorectal cancer: Current therapies, biomarker refinement, and emerging strategies. Drugs 2026;86(1):37-57. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, hematology-oncology fellows, surgeons and other healthcare providers involved in the treatment of colorectal cancer.

LEARNING OBJECTIVES

• Develop an understanding of validated biomarkers of response in CRC, such as RAS mutations, microsatellite instability (MSI)/mismatch repair (MMR) deficiency, HER2 overexpression and BRAF V600E mutations, and consider the implications for molecular testing and clinical care.
• Optimize the use of neoadjuvant and adjuvant systemic therapy for patients with localized CRC, considering various clinical and biological factors, such as age, performance status, disease stage and MSI/MMR status, and the potential relevance of molecular residual disease.
• Formulate a plan to guide the selection and sequencing of therapy for patients diagnosed with metastatic CRC (mCRC), accounting for tumor sidedness, biomarker profile, prior systemic therapy, symptomatology and personal goals of treatment.
• Evaluate the biological rationale for the use of immune checkpoint inhibitors in the treatment of localized and advanced MSI-high/MMR-deficient CRC, and counsel patients regarding evidence-based and guideline-endorsed treatment recommendations.
• Appreciate published research documenting the efficacy of targeted therapeutic approaches for patients with mCRC and various actionable genomic alterations, and use this information to personalize treatment recommendations.
• Recall ongoing trials evaluating novel agents and strategies for CRC, and use this information to refer patients for study participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 2.25 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/ASCO2025/CRC/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Andrea Cercek, MD
Section Head, Colorectal Cancer
Co-Director, Center for Young Onset Colorectal and Gastrointestinal Cancers
Attending, Gastrointestinal Oncology Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York

Advisory Boards: 3T Biosciences, AbbVie Inc, Agents, Amgen Inc, Daiichi Sankyo Inc, GSK, Janssen Biotech Inc, Merck, Pfizer Inc, Regeneron Pharmaceuticals Inc, Roche Laboratories Inc, Summit Therapeutics, UroGen Pharma; Contracted Research: GSK, Pfizer Inc.

Arvind Dasari, MD, MS
Professor
Department of Gastrointestinal Medical Oncology
The University of Texas MD Anderson Cancer Center
Houston, Texas

Advisory Committees: Agenus Inc, Bristol Myers Squibb, Exelixis Inc, Illumina, Lantheus, Personalis, Sanofi, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Bristol Myers Squibb, Crinetics Pharmaceuticals, Eisai Inc, Enterome, Guardant Health, Hutchison MediPharma, Natera Inc, NeoGenomics, Personalis, RayzeBio Inc, Taiho Oncology Inc, Xencor.

Pashtoon Kasi, MD, MS
Medical Director of GI Oncology
Endowed Rad Family Chair in Gastrointestinal Oncology
Associate Professor
Department of Medical Oncology and Therapeutics Research
City of Hope Orange County
Irvine, California

Advisory Committees: Elicio Therapeutics; Consulting Agreements: Agenus Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Bexion Pharmaceuticals, BostonGene, Daiichi Sankyo Inc, Delcath Systems Inc, Eisai Inc, Exact Sciences Corporation, Foundation Medicine, Guardant Health, Illumina, Lilly, Merck, MSD, Natera Inc, NeoGenomics, QED Therapeutics, Regeneron Pharmaceuticals Inc, SAGA Diagnostics, Seagen Inc, Servier Pharmaceuticals LLC, Taiho Oncology Inc, Tempus, Xilio Therapeutics; Contracted Research: Agenus Inc, Merck, Novartis; Stock Options/Stock — Public Companies: Elicio Therapeutics.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Advisory Committees: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia AB (CANFOUR trial), Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Galapagos NV, GSK, Hookipa Pharma Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Lilly, Merck KGaA, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Pfizer Inc, Pierre Fabre, Roche Laboratories Inc, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation; Nonrelevant Financial Relationships: Bexon Clinical Consulting.

MODERATOR
J Randolph Hecht, MD
Professor of Clinical Medicine
Director, UCLA GI Oncology Program
Carol and Saul Rosenzweig Chair in Cancer Therapies
Development
UCLA David Geffen School of Medicine
Santa Monica, California

Advisory Committees: Actym Therapeutics, MBQ Pharma, Radical AI, Triumvira Immunologics; Consulting Agreements: BeiGene Ltd, Hexagon Bio, Parabilis Medicines, Revolution Medicines, UroGen Pharma, Xilio Therapeutics; Contracted Research: A2 Bio, Affini-T Therapeutics, Agenus Inc, AstraZeneca Pharmaceuticals LP, Bold Therapeutics, Camurus, CG Invites, Crinetics Pharmaceuticals, Exelixis Inc, Gilead Sciences Inc, Gritstone bio, GSK, IGM Biosciences Inc, Janssen Biotech Inc, Mirati Therapeutics Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines, Tizona Therapeutics Inc, Xilio Therapeutics; Stock Options — Private Companies: Actym Therapeutics, Radical AI, Triumvira Immunologics.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from GSK and Natera Inc.

Release date: June 2025
Expiration date: June 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Dasari

Bando H et al. A randomized, double-blind, phase III study comparing trifluridine/tipiracil (FTD/TPI) versus placebo in patients with molecular residual disease following curative resection of colorectal cancer (CRC): The ALTAIR study. Gastrointestinal Cancers Symposium 2025;Abstract LBA22.

Fidyk E et al. Real-world ctDNA testing patterns, associated biomarkers and sites of metastasis in early stage colorectal cancer. ASCO 2024;Abstract 3610.

Kasi PM et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study. Gastrointestinal Cancers Symposium 2024;Abstract 9.

Kasi PM et al. Impact of circulating tumor DNA-based detection of molecular residual disease on the conduct and design of clinical trials for solid tumors. JCO Precis Oncol 2022;6. Abstract

Kotani D et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med 2023;29(1):127-34. Abstract

Maddalena G et al. INTERCEPT program of circulating tumor DNA (ctDNA) testing for minimal residual disease (MRD) in colorectal cancer (CRC): Results from a prospective clinical cohort. Gastrointestinal Cancers Symposium 2024;Abstract 27.

Meyerhardt et al. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage III colon cancer: The CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA 2021;325(13):1277-86. Abstract

Nakamura Y et al. ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nat Med 2024;30(11):3272-83. Abstract

Nowak JA et al. Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: Findings from CALGB (Alliance)/SWOG 80702. Gastrointestinal Cancers Symposium 2025;Abstract LBA14.

Tie J et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: Overall survival and updated 5-year results from the randomized DYNAMIC trial. ASCO 2024;Abstract 108.

 

Dr Cercek

Cercek A et al. Nonoperative management of mismatch repair-deficient tumors. N Engl J Med 2025;[Online ahead of print]. Abstract

Chalabi M et al. Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer. N Engl J Med 2024;390(21):1949-58. Abstract

Chalabi M et al. Neoadjuvant immunotherapy in locally advanced MMR-deficient colon cancer: 3-year disease-free survival from NICHE-2. ESMO 2024;Abstract LBA24.

Chalabi M et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 2020;26(4):566-76. Abstract

Hu H et al. Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): A single-centre, parallel-group, non-comparative, randomised, phase 2 trial. Lancet Gastroenterol Hepatol 2022;7(1):38-48. Abstract

Kasi A et al. A phase II open-label study of sacituzumab govitecan in patients with previously treated locally advanced, recurrent, or metastatic cholangiocarcinoma (SIGNA). Gastrointestinal Cancers Symposium 2025;Abstract TPS651.

Ludford K et al. Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors. J Clin Oncol 2023;41(12):2181-90. Abstract

Rousseau B et al. The duration of immunotherapy for mismatch repair-deficient cancers. N Engl J Med 2025;392(8):824-26. Abstract

 

Dr Kasi

Adam R et al. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): Results from a multicentre, open-label, prospective, randomised controlled trial. Lancet 2024;404(10458):1107-18. Abstract

Bridgewater JA et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): Long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2020;21(3):398-411. Abstract

Dekker E et al. Colorectal cancer. Lancet 2019;394(10207):1467-80. Abstract

Hitchcock KE et al. Alliance for clinical trials in oncology (Alliance) trial A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: Evaluating radiation, ablation, and surgery (ERASur). Res Sq [Preprint] 2023;rs.3.rs-3773522. Abstract

Kasi PM et al. Use of circulating tumor DNA (ctDNA) for early assessment of treatment response in patients with advanced colorectal cancer (aCRC): A real-world (RW) analysis. Gastrointestinal Cancers Symposium 2023;Abstract 246.

Malla M et al. Using circulating tumor DNA in colorectal cancer: Current and evolving practices. J Clin Oncol 2022;40(24):2846-57. Abstract

Nakamura Y et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med 2020;26(12):1859-64. Abstract

Sangaré L et al. An evaluation of RAS testing among metastatic colorectal cancer patients in the USA. Future Oncol 2021;17(13):1653-63. Abstract

Shitara K et al. Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial. Gastrointestinal Cancers Symposium 2023;Abstract 11.

 

Dr Hecht

André T et al. Pembrolizumab versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase III KEYNOTE-177 study. Ann Oncol 2025;36(3):277-84. Abstract

André T et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. Gastrointestinal Cancers Symposium 2024;Abstract LBA768.

André T et al. Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer. N Engl J Med 2024;391(21):2014-26. Abstract

André T et al. Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair deficient solid tumors. JAMA Netw Open 2023;6(11). Abstract

André T et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol 2022;33(10):1052-60. Abstract

Le DT et al. Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: Final analysis of KEYNOTE-164. Eur J Cancer 2023;186:185-95. Abstract

Le DT et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372(26):2509-20. Abstract

Lenz HJ et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) or NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Expanded analyses from CheckMate 8HW. ASCO 2025;Abstract 3501.

Lenz HJ et al. First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: The phase II CheckMate 142 study. J Clin Oncol 2022;40(2):161-70. Abstract

Nasca V et al. Association of immune-related adverse events with the outcomes of immune checkpoint inhibitors in patients with dMMR/MSI-H metastatic colorectal cancer. J Immunother Cancer 2023;11(1). Abstract

Picco G et al. Novel WRN helicase inhibitors selectively target microsatellite-unstable cancer cells. Cancer Discov 2024;14(8):1457-75. Abstract

Schneider BJ et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol 2021;39(36):4073-126. Abstract

 

Prof Van Cutsem

Desai J et al. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: A phase 1b trial. Nat Med 2024;30(1):271-8. Abstract

Fakih MG et al. Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C. N Engl J Med 2023;389(23):2125-39. Abstract

Kopetz S et al. BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer. Gastrointestinal Cancers Symposium 2025;Abstract 16.

Kopetz S et al. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: A randomized phase 3 trial. Nat Med 2025;31(3):901-8. Abstract

Napolitano S et al. Targeting the EGFR signalling pathway in metastatic colorectal cancer. Lancet Gastroenterol Hepatol 2024;9(7):664-76. Abstract

Pietrantonio F et al. Overall survival analysis of the phase III CodeBreaK 300 study of sotorasib plus panitumumab versus investigator’s choice in chemorefractory KRAS G12C colorectal cancer. J Clin Oncol 2025;JCO2402026. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial.Lancet Oncol 2016;17(6):738-46. Abstract

Siena S et al. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: Biomarker analyses of DESTINY-CRC01. Nat Commun 2024;15(1):10213. Abstract

Siena S et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): A multicentre, open-label, phase 2 trial. Lancet Oncol 2021;22(6):779-89. Abstract

Siena S et al. Breaking barriers in HER2+ cancers. Cancer Cell 2020;38(3):317-19. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Strickler JH et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): A multicentre, open-label, phase 2 study. Lancet Oncol 2023;24(5):496-508. Abstract

Van Cutsem E et al. ANCHOR CRC: Results from a single-arm, phase II study of encorafenib plus binimetinib and cetuximab in previously untreated BRAF^V600E-mutant metastatic colorectal cancer. J Clin Oncol 2023;41(14):2628-37. Abstract

Yaeger R et al. Efficacy and safety of adagrasib plus cetuximab in patients with KRASG12C-mutated metastatic colorectal cancer. Cancer Discov 2024;14(6):982-993. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, hematology-oncology fellows, surgeons and other healthcare providers involved in the treatment of colorectal cancer.

LEARNING OBJECTIVES

• Develop an understanding of validated biomarkers of response in CRC, such as RAS mutations, microsatellite instability (MSI)/mismatch repair (MMR) deficiency, HER2 overexpression and BRAF V600E mutations, and consider the implications for molecular testing and clinical care.
• Optimize the use of neoadjuvant and adjuvant systemic therapy for patients with localized CRC, considering various clinical and biological factors such as age, performance status, disease stage, MSI/MMR status and the potential relevance of molecular residual disease.
• Formulate a plan to guide the selection and sequencing of therapy for patients with metastatic CRC (mCRC), accounting for tumor sidedness, biomarker profile, prior systemic therapy, symptomatology and personal goals of treatment.
• Evaluate the biological rationale for the use of immune checkpoint inhibitors in the treatment of MSI-high/MMR-deficient localized or advanced CRC, and counsel patients regarding evidence-based and guideline-endorsed therapy recommendations.
• Appreciate published and emerging research documenting the efficacy of BRAF/EGFR inhibition for newly diagnosed or relapsed/refractory mCRC with a BRAF V600E mutation, and optimally incorporate this therapeutic strategy into patient care.
• Recognize available data with HER2-targeted therapies for HER2-positive mCRC, and consider the current role of FDA-approved approaches.
• Apply available research to optimize the selection and sequencing of therapy for patients with mCRC and a KRAS G12C mutation, considering the implications of recent clinical trial findings and regulatory actions.
• Recall ongoing trials evaluating novel biomarker-directed agents and strategies for CRC, and use this information to appropriately refer patients for study participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
CME credit is no longer available for this issue

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
CME credit is no longer available for this issue

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/ASCOGI25/CRC/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Arvind Dasari, MD, MS
Professor
Department of Gastrointestinal Medical Oncology
The University of Texas MD Anderson Cancer Center
Houston, Texas

Consulting Agreements: Bristol Myers Squibb, Exelixis Inc, Illumina, Lantheus, Personalis, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Eisai Inc, Enterome, Guardant Health, Hutchison MediPharma, Natera Inc, NeoGenomics, Personalis, Taiho Oncology Inc, Xencor.

Van K Morris, MD
Associate Professor
Department of Gastrointestinal Medical Oncology
The University of Texas MD Anderson Cancer Center
Houston, Texas

Advisory Committees: AmMax Bio, Bristol Myers Squibb, Incyte Corporation, Pfizer Inc, Scandion Oncology; Contracted Research: AmMax Bio, Bicara Therapeutics, BioNTech SE, Bristol Myers Squibb, Pfizer Inc.

Jenny Seligmann, MBChB, PhD
Professor of Gastrointestinal Cancer
University of Leeds
Leeds, United Kingdom

Advisory Committees: Bristol Myers Squibb, GSK, Merck Serono, Nanobiotix, Sanofi, Servier Pharmaceuticals LLC; Contracted Research: GSK, Merck Serono, Pierre Fabre, Roche Diagnostics; Data and Safety Monitoring Boards/Committees: GSK; Speakers Bureaus: Bayer HealthCare Pharmaceuticals, GSK, Merck Serono, Servier Pharmaceuticals LLC.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Advisory Committees: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia AB (CANFOUR trial), Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Galapagos NV, GSK, Hookipa Pharma Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Lilly, Merck KGaA, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Pfizer Inc, Pierre Fabre, Roche Laboratories Inc, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation; Nonrelevant Financial Relationships: Bexon Clinical Consulting.

MODERATOR
Christopher Lieu, MD
Professor of Medicine
Associate Director for Clinical Research
Co-Director, GI Medical Oncology
University of Colorado Cancer Center
Aurora, Colorado

Consulting Agreements: Amgen Inc, Pfizer Inc; Contracted Research: Genentech, a member of the Roche Group, Sanofi.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from GSK, Natera Inc, and Pfizer Inc.

Release date: February 2025
Expiration date: February 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Dasari

Dasari A et al. ctDNA applications and integration in colorectal cancer: An NCI Colon and rectal-anal task forces whitepaper. Nat Rev Clin Oncol 2020;17(12):757-70. Abstract

Kasi PM et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study. Gastrointestinal Cancers Symposium 2024;Abstract 9.

Maddalena G et al. INTERCEPT program of circulating tumor DNA (ctDNA) testing for minimal residual disease (MRD) in colorectal cancer (CRC): Results from a prospective clinical cohort. ASCO Gastrointestinal Cancers Symposium 2024;Abstract 27.

Nakamura Y et al. ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nat Med 2024;30(11):3272-83. Abstract

Phan TG, Croucher PI. The dormant cancer cell life cycle. Nat Rev Cancer 2020;20(7):398-411. Abstract

Taieb J et al. Combined analyses of ctDNA and Immunoscore in stage III colon cancer patients: A post hoc analysis of the IDEA-France and -Greece trials. ESMO Gastrointestinal Oncology 2024;Abstract 7MO.

Tie J et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: Overall survival and updated 5-year results from the randomized DYNAMIC trial. ASCO 2024;Abstract 108.

Tie J et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med 2022;386(24):2261-72. Abstract

Yukami H et al. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. Gastrointestinal Cancers Symposium 2024;Abstract 6.

 

Dr Morris

André T et al. Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer. N Engl J Med 2024;391(21):2014-26. Abstract

André T et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 2020;383(23):2207-18. Abstract

Kopetz S et al. BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer. Gastrointestinal Cancers Symposium 2025;Abstract 16.

Kopetz S et al. Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. Nat Med 2024;30(11):3261-71. Abstract

Kopetz S et al. Encorafenib, binimetinib, and cetuximab in BRAFV600E-mutated colorectal cancer. N Engl J Med 2019;381(17):1632-43. Abstract

Pan K et al. Phase I/II trial of encorafenib, cetuximab, and nivolumab in microsatellite stable BRAF^V600E metastatic colorectal cancer following progression on prior BRAF+EGFR targeted therapies. Gastrointestinal Cancers Symposium 2025;Abstract 182.

Shiu K-K et al. Pembrolizumab versus chemotherapy in microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): 5-year follow-up of the randomized phase III KEYNOTE-177 study. ESMO 2023;Abstract LBA32.

Tabernero J et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: Updated survival results and subgroup analyses from the BEACON study. J Clin Oncol 2021;39(4):273-84. Abstract

Tian J et al. Combined PD-1, BRAF and MEK inhibition in BRAF^V600E colorectal cancer: A phase 2 trial. Nat Med 2023;29(2):458-66. Abstract

Van Cutsem E et al. ANCHOR CRC: Results from a single-arm, phase II study of encorafenib plus binimetinib and cetuximab in previously untreated BRAF^V600E-mutant metastatic colorectal cancer. J Clin Oncol 2023;41(14):2628-37. Abstract

 

Dr Seligman

André T et al. Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). ASCO 2021;Abstract 3500.

Cercek A et al. Durable complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer. ASCO 2024;Abstract LBA3512.

Cercek A et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022;386(25):2363-76. Abstract

Cervantes A et al. Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2023;34(1):10-32. Abstract

Chalabi M et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 2020;26(4):566-76. Abstract

Diaz LA Jr et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): Final analysis of a randomised, open-label, phase 3 study. Lancet Oncol 2022;23(5):659-70. Abstract

Elez E et al. SEAMARK: Phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAF V600E-mutant mCRC. Future Oncol 2024;20(11):653-63. Abstract

Sinicrope FA et al. Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient mismatch repair (ATOMIC, Alliance A021502). ASCO 2019;Abstract e15169.

 

Prof Van Cutsem

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Siena S et al. HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: Biomarker analyses of DESTINY-CRC01. Nat Commun 2024;15(1):10213. Abstract

Siena S et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): A multicentre, open-label, phase 2 trial. Lancet Oncol 2021;22(6):779-89. Abstract

Siena S et al. Breaking barriers in HER2+ cancers. C Cancer Cell 2020;38(3):317-9. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2024:1-9. Abstract

Strickler JH et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): A multicentre, open-label, phase 2 study. Lancet Oncol 2023;24(5):496-508. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract

 

Dr Lieu

Fakih MG et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRASG12C-mutated metastatic colorectal cancer (mCRC). ASCO 2024;Abstract LBA3510.

Fakih MG et al.Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C. N Engl J Med 2023;389(23):2125-39. Abstract

Fakih MG et al. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): A prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol 2022;23(1):115-24. Abstract

Hong DS et al. Sotorasib (soto) plus panitumumab (Pmab) and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreaK 101 phase 1b safety and efficacy. ASCO 2023;Abstract 3513.

Ji J et al. Targeting KRAS^G12C-mutated advanced colorectal cancer: Research and clinical developments. Onco Targets Ther 2022:15:747-56. Abstract

Kopetz S et al. KRYSTAL-1: Pooled phase 1/2 efficacy and safety of adagrasib (MRTX849) in combination with cetuximab in patients with metastatic colorectal cancer (CRC) harboring a KRAS^G12C mutation. AACR 2024;Abstract CT013.

Ottaiano A et al. KRAS p.G12C mutation in metastatic colorectal cancer: Prognostic implications and advancements in targeted therapies. Cancers 2023;15(14):3579. Abstract

Qunaj L et al. Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer. Front Oncol 2023:13;1252516. Abstract

Ryan MB et al. KRAS^G12C-independent feedback activation of wild-type RAS constrains KRAS^G12C inhibitor efficacy. Cell Rep 2022;39(12):110993. Abstract

Sacher A et al. Single-agent divarasib (GDC-6036) in solid tumors with a KRAS G12C mutation. N Engl J Med 2023;389(8):710-21. Abstract

Siena S et al. Sotorasib (soto), panitumumab (pani) and FOLFIRI in the first-line (1L) setting for KRAS G12C–mutated metastatic colorectal cancer (mCRC): Safety and efficacy analysis from the phase Ib CodeBreaK 101 study. ESMO 2024;Abstract 505O.

Weiss J et al. KRYSTAL-1: Adagrasib (MRTX849) as monotherapy or combined with cetuximab (Cetux) in patients (pts) with colorectal cancer (CRC) harboring a KRASG12C mutation. ESMO 2021;Abstract LBA6.

Yaeger R et al. Efficacy and safety of adagrasib plus cetuximab in patients with KRASG12C-mutated metastatic colorectal cancer. Cancer Discov 2024;14(6):982-93. Abstract

Yaeger R et al. Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C. N Engl J Med 2023;388(1):44-54. Abstract