Investigators Discuss Available Research Guiding the Care of Patients with Colorectal Cancer — Symposium Video Proceedings

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.

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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.

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

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

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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.

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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