Faculty

TARGET AUDIENCE
This program is intended for urologists, medical and radiation oncologists and other allied healthcare professionals involved in the treatment of prostate cancer.

LEARNING OBJECTIVES

• Appreciate the incidence and clinical relevance of PTEN deficiency in prostate cancer, and understand the optimal method for assessing PTEN status in patients.
• Evaluate emerging Phase III data with combined AKT and androgen biosynthesis inhibition for patients with metastatic hormone-sensitive prostate cancer and PTEN deficiency, and consider the potential role of this form of therapy in the current treatment algorithm.
• Implement a plan of care to recognize and manage side effects and toxicities associated with AKT inhibitors in preparation for their potential availability for patients with prostate cancer.
• Recall the design of ongoing clinical trials evaluating novel AKT inhibitors in combination with standard therapies for metastatic prostate cancer, and appropriately counsel 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
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) — CONTINUOUS 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
CME credit is no longer available for this issue.

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:

Leonard G Gomella, MD
The Bernard W Godwin Professor of Prostate Cancer
Chairman, Department of Urology
Senior Director, Clinical Affairs, Sidney Kimmel Cancer Center
Enterprise VP for Urology, Jefferson Health
Editor-in-Chief, Canadian Journal of Urology International
Thomas Jefferson University
Philadelphia, Pennsylvania

Advisory Committees: AstraZeneca Pharmaceuticals LP, Ferring Pharmaceuticals, Lantheus, Merck; Patents: Through Thomas Jefferson University.

Evan Y Yu, MD
Section Head, Medical Oncology, Clinical Research Division
Fred Hutchinson Cancer Center
Medical Director, Clinical Research Support
Fred Hutchinson Cancer Research Consortium
Professor of Medicine
Division of Hematology and Oncology, Department of Medicine
University of Washington School of Medicine
Seattle, Washington

Advisory Committees: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Johnson & Johnson Pharmaceuticals, Lantheus, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Oncternal Therapeutics, Tolmar; Contracted Research: Bayer HealthCare Pharmaceuticals, Blue Earth Diagnostics, Dendreon Pharmaceuticals Inc, Lantheus, Merck, Oncternal Therapeutics, Seagen Inc, Tyra Biosciences Inc.

MODERATOR
Daniel George, MD
Eleanor Easley Distinguished Chair
Professor of Medicine, Surgery and Urology
Duke University School of Medicine
ACS Research Professor
Co-Lead, DCI Center for Prostate and Urologic Cancers
Duke Cancer Institute
Durham, North Carolina

Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Cardinal Health, Novartis, Pfizer Inc; Consulting Agreements: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Exelixis Inc, Johnson & Johnson Pharmaceuticals, Merck, Novartis; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Corvus Pharmaceuticals, Exelixis Inc, Merck, Novartis, Pfizer Inc; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP; Nonrelevant Financial Relationships: IDEOlogy Health, MJH Life Sciences, Targeted Oncology, UpToDate, UroToday.

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 grantor.

These activities are supported by an educational grant from AstraZeneca Pharmaceuticals LP.

Release date: May 2025
Expiration date: May 2026

Dr Gomella

Agarwal N et al. Orteronel for metastatic hormone-sensitive prostate cancer: A multicenter, randomized, open-label phase III trial (SWOG-1216). J Clin Oncol 2022;40(28):3301-9. Abstract

Armstrong AJ et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2022;40(15):1616-22. Abstract

Chi KN et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: Final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-303. Abstract

Clarke NW et al. Corrigendum to addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: Long-term survival results from the STAMPEDE trial. Ann Oncol 2020;31(3):442. Abstract

Fizazi K et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2022;399(10336):1695-707. Abstract

Fizazi K et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): Final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 2019;20(5):686-700. Abstract

Freedland SJ et al. Reasons for oncologist and urologist treatment choice in metastatic castration-sensitive prostate cancer (mCSPC): A physician survey linked to patient chart reviews in the United States. ASCO 2022;Abstract 5065.

Freedland SJ et al. Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration. Cancer Med 2021;10(23):8570-80. Abstract

Gravis G et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: Further analyses of CHAARTED and GETUG-AFU15 studies. Eur Urol 2018;73(6):847-55. Abstract

James ND et al. Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 2022;151(3):422-34. Abstract

Kyriakopoulos CE et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018;36(11):1080-7. Abstract

Scher HI et al. Trial design and objectives for castration-resistant prostate cancer: Updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol 2016;34(12):1402-18. Abstract

Smith MR et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 2022;386(12):1132-42. Abstract

 

Dr Yu

Cetintas VB, Batada NN. Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment? J Transl Med 2020;18(1):45. Abstract

Crabb SJ et al. CAPItello-280: A phase III study of capivasertib and docetaxel versus placebo and docetaxel in metastatic castration-resistant prostate cancer. Genitourinary Cancers Symposium 2023;Abstract TPS287.

Crabb SJ et al. Overall survival update for patients with metastatic castration-resistant prostate cancer treated with capivasertib and docetaxel in the phase 2 ProCAID clinical trial. Eur Urol 2022;82(5):512-5. Abstract

de Bono J et al. IPATential150: Phase III study of ipatasertib (ipat) plus abiraterone (abi) vs placebo (pbo) plus abi in metastatic castration-resistant prostate cancer (mCRPC). ESMO 2020;Abstract LBA4.

Esteban-Villarrubia J et al. Mechanisms of immune evasion in PTEN loss prostate cancer. Immuno 2024;4(4):444-60. Abstract

Gonzalez Velez M et al. Differential impact of tumor suppressor gene (TP53, PTEN, RB1) alterations and treatment outcomes in metastatic, hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis 2022;25(3):479-83. Abstract

Gupta S et al. Real-world overall survival and treatment patterns by PTEN status in metastatic castration-resistant prostate cancer. JCO Precis Oncol 2024;8. Abstract

Lotan TL et al. PTEN loss detection in prostate cancer: Comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget 2017;8(39):65566-76. Abstract

Nizialek E et al. Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone-sensitive prostate cancer. Prostate 2021;81(9):572-9. Abstract

Shore ND et al. A phase I study of capivasertib in combination with abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Genitourinary Cancers Symposium 2021;Abstract 85.

Stopsack KH et al. Oncogenic genomic alterations, clinical phenotypes, and outcomes in metastatic castration-sensitive prostate cancer. Clin Cancer Res. 2020 Jul 1;26(13):3230-3238. Abstract

Turnham DJ et al. The PTEN conundrum: How to target PTEN-deficient prostate cancer. Cells 2020;9(11):2342. Abstract

Zhang J-Y et al. Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer. Asian J Androl 2021;24(1):50-5. Abstract

 

Dr George

Sweeney C et al. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): A multicentre, randomised, double-blind, phase 3 trial. Lancet 2021;398(10295):131-42. Abstract

Turner N et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the Phase III CAPItello-291 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-04.

Zhang J et al. A phase I study of the pharmacokinetics and safety of ipatasertib, an Akt inhibitor in Chinese patients with locally advanced or metastatic solid tumors. Clin Ther 2025;47(2):128-34. Abstract

Faculty

TARGET AUDIENCE
This activity is intended for gynecologic oncologists, medical oncologists, gynecologists and other healthcare providers involved in the treatment of ovarian cancer.

LEARNING OBJECTIVES

• Understand available clinical research findings with PARP inhibitors as maintenance therapy after first-line platinum-based chemotherapy for advanced ovarian cancer (OC), and as appropriate, counsel patients regarding personalized treatment recommendations.
• Assess available clinical trial data with and newly adapted indications for FDA-endorsed PARP inhibitors for patients with recurrent, platinum-sensitive and multiregimen-refractory OC to optimally and appropriately incorporate these agents into management algorithms.
• Evaluate the biological rationale for and published research data with PARP inhibitors in combination with other systemic therapies, and consider the current and future clinical and research implications of these findings for OC management.
• Appraise relevant biological and patient- and treatment-related factors to individualize the selection and sequencing of therapy for platinum-sensitive and platinum-resistant recurrent OC.
• Recognize the rationale for targeting folate receptor alpha (FRα) in OC, and determine effective methods to test for this newly relevant biomarker.
• Understand the mechanism of action of and current research findings with antibody-drug conjugates directed at FRα, and optimally integrate these agents into the care of patients with recurrent OC.
• Appreciate side effects associated with various systemic therapies commonly employed in the management of OC, and use this information to develop supportive care plans for patients undergoing treatment with these agents.
• Recall the design of ongoing clinical trials evaluating novel agents and strategies for OC, and as appropriate, counsel patients about availability and 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
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 component and a post-test, 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, this program has 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, this program has 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/SGO25Ovarian/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:

Kathleen N Moore, MD, MS
Deputy Director
Virginia Kerley Cade Chair in Developmental Therapeutics
Co-Director, Cancer Therapeutics Program
Stephenson Cancer Center at the University of Oklahoma HSC
Associate Director, GOG Partners
Board of Directors, GOG Foundation
Board of Directors, ASCO
Oklahoma City, Oklahoma

Advisory Committees: Aadi Bioscience, AbbVie Inc, AstraZeneca Pharmaceuticals LP, BioNTech SE, Blueprint Medicines, Caris Life Sciences, Corcept Therapeutics, Daiichi Sankyo Inc, Duality Biologics, Eisai Inc, Genentech, a member of the Roche Group, GSK, ImmunoGen Inc, Janssen Biotech Inc, Lilly, Merck, Mersana Therapeutics Inc, Novartis, Regeneron Pharmaceuticals Inc, Schrödinger, Takeda Pharmaceuticals USA Inc, Verastem Inc, Zentalis Pharmaceuticals, Zymeworks Inc; Contracted Research: Allarity Therapeutics, Daiichi Sankyo Inc, GSK, ImmunoGen Inc, Schrödinger, Verastem Inc; Data and Safety Monitoring Boards/Committees: Bicycle Therapeutics.

Ritu Salani, MD, MBA
Director, Division of Gynecologic Oncology
Professor, Department of Obstetrics and Gynecology
David Geffen School of Medicine at UCLA
Los Angeles, California

Advisory Committees: AbbVie Inc, Daiichi Sankyo Inc, Eisai Inc, Genmab US Inc, GSK, Merck, Pfizer Inc; Nonrelevant Financial Relationships: Elsevier, UpToDate.

Shannon N Westin, MD, MPH, FASCO, FACOG
Professor
Medical Director, Gynecologic Oncology Center
Director, Early Drug Development
Department of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Houston, Texas

Consulting Agreements: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Caris Life Sciences, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo Inc, Eisai Inc, EQRx, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Immunocore, ImmunoGen Inc, Incyte Corporation, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Mereo BioPharma, Mersana Therapeutics Inc, NGM Biopharmaceuticals, Nuvectis Pharma Inc, Pfizer Inc, pharmaand GmbH, Seagen Inc, Verastem Inc, Vincerx Pharma, Zentalis Pharmaceuticals, ZielBio; Contracted Research (to Institution): AstraZeneca Pharmaceuticals LP, Avenge Bio, Bayer HealthCare Pharmaceuticals, Bio-Path Holdings Inc, Clovis Oncology, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, GSK, Jazz Pharmaceuticals Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Mereo BioPharma, Novartis, Nuvectis Pharma Inc, Pfizer Inc, pharmaand GmbH, Zentalis Pharmaceuticals.

MODERATOR
Angeles Alvarez Secord, MD, MHSc
Professor of Obstetrics and Gynecology, Gynecologic Oncology
Director of Gynecologic Oncology Clinical Trials
Duke Cancer Institute
Durham, North Carolina

Advisory Boards (Honoraria): AbbVie Inc; Advisory Boards (Uncompensated): AstraZeneca Pharmaceuticals LP, CanariaBio Inc, Clovis Oncology, Gilead Sciences Inc, GSK, ImmunoGen Inc, Imvax Inc, Merck, Mersana Therapeutics Inc, Natera Inc, OncoQuest Inc; Clinical Trial Steering Committees (Uncompensated): CanariaBio Inc (FLORA-5 trial, QPT-ORE-004 trial), VBL Therapeutics (OVAL trial); Clinical Trial and Research Grant Funding (to Institution): AbbVie Inc, Aravive Inc, AstraZeneca Pharmaceuticals LP, Clovis Oncology, Eisai Inc, Ellipses Pharma, Genentech, a member of the Roche Group, GSK, I-Mab Biopharma, ImmunoGen Inc, Karyopharm Therapeutics, Merck, Mersana Therapeutics Inc, Myriad Genetic Laboratories Inc, OncoQuest Inc, Seagen Inc, VBL Therapeutics, Zentalis Pharmaceuticals; Nonrelevant Financial Relationships: GOG Foundation, Foundation for Women’s Cancer, National Clinical Trials Network, NRG Oncology, Society of Gynecologic Oncology, UpToDate.

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 AbbVie Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Merck, and Mural Oncology Inc.

Release date: April 2025
Expiration date: April 2026

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

Dr Westin

Banerjee S et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021;22(12):1721-31. Abstract

Bradley W et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO1. SGO 2021;Abstract.

Colombo N et al. Maintenance olaparib + bevacizumab (bev) in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): RECIST and/or CA-125 objective response rate (ORR) in the phase III PAOLA-1 trial. ESMO 2020;Abstract 812MO.

DiSilvestro P et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: The SOLO1/GOG 3004 trial. J Clin Oncol 2023;41(3):609-17. Abstract

DiSilvestro P et al. Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial. ESMO 2022;Abstract 517MO.

DiSilvestro P et al. Efficacy of maintenance olaparib for patients with newly diagnosed advanced ovarian cancer with a BRCA mutation: Subgroup analysis findings from the SOLO1 trial. J Clin Oncol 2020;38(30):3528-37. Abstract

González-Martin A et al. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2023;34(10):833-48. Abstract

Harter P et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): Results from the randomized, placebo (pbo)-controlled phase III DUO-O trial. ASCO 2023;Abstract LBA5506.

Hettle R et al. Population-adjusted indirect treatment comparison (PAITC) of maintenance PARP inhibitor (PARPi) with or without bevacizumab versus bevacizumab in women with newly diagnosed ovarian cancer (OC). ASCO 2020;Abstract 6052.

Monk BJ et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: Final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol 2024;35(11):981-92. Abstract

Monk BJ et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol 2022;40(34):3952-64. Abstract

Ray-Coquard I et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: Final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol 2023;34(8):681-92. Abstract

Trillsch F et al. Durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) for newly diagnosed advanced ovarian cancer (AOC) without a tumour BRCA1/BRCA2 mutation (non-tBRCAm): Updated results from DUO-O. ESMO Gynaecological Cancers Congress 2024;Abstract 430.

Vergote I et al. Chemotherapy with or without pembrolizumab followed by maintenance with olaparib or placebo for first-line treatment of advanced BRCA non-mutated epithelial ovarian cancer: Results from the randomized phase 3 ENGOT-OV43/GOG-3036/KEYLYNK-001 study. ESGO 2025;Abstract 128.

 

Dr Secord

Alvarez Secord A et al. The efficacy and safety of mirvetuximab soravtansine in FRa-positive, third- line and later, recurrent platinum-sensitive ovarian cancer: The single-arm phase II PICCOLO trial. Ann Oncol 2025;36(3):321-30. Abstract

Bello D et al. Phase 3 MIRASOL (GOG 3045/ENGOT-ov55) trial: Mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in older patients with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression. ASCO 2024;Abstract 5580.

Hilpert F et al. Quality-adjusted time without symptoms of disease progression or toxicity analysis of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in folate receptor-alpha positive, platinum-resistant ovarian cancer. ESGO 2025;Abstract 1089.

Ivanova M et al. Standardized pathology report for HER2 testing in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer. Virchows Arch 2024;484(1):3-14. Abstract

Konecny G et al. Patient-reported outcome results from phase III MIRASOL trial of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in FRα-positive, platinum-resistant ovarian cancer. SGO 2024;Abstract 08.

Lee D et al. HER2 expression in ovarian cancer: Its relationship with HRD status, and other biomarkers. ESMO 2024;Abstract 765P.

Lee EK et al. A phase I/II study of rinatabart sesutecan (Rina-S) in patients with advanced ovarian or endometrial cancer. ESMO 2024;Abstract 719MO.

Lee J-M et al. Cediranib and olaparib combination compared with cediranib or olaparib alone, or chemotherapy in platinum-resistant or primary platinum-refractory ovarian cancer: NRG-GY005. J Clin Oncol 2024;42(36):4305-16. Abstract

Liu YL et al. Olaparib as treatment for platinum‐sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis. Cancer 2025;131(2):e35707. Abstract

Martin LP et al. Luveltamab tazevibulin, an antifolate receptor alpha (FRα) antibody-drug conjugate (ADC), in combination with bevacizumab (bev) in patients with recurrent high-grade epithelial ovarian cancer (EOC): STRO-002-GM2 phase I study. ESMO 2024;Abstract 749P.

Matulonis UA et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: Results from the SORAYA study. J Clin Oncol 2023;41(13):2436-45. Abstract

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

Oaknin A et al. Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolRα) antibody drug conjugate (ADC), safety and efficacy in a broad distribution of FolRα expression in patients with recurrent epithelial ovarian cancer (OC): Update of STRO-002-GM1 phase 1 dose expansion cohort. ASCO 2023;Abstract 5508.

Van Gorp T et al. Final overall survival analysis among patients with FRα-positive, platinum-resistant ovarian cancer (PROC) treated with mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in the Phase 3 MIRASOL (GOG 3045/ENGOT-ov55) study. SGO 2025;Abstract 939696.

 

Dr Moore

Colombo R et al. The journey of antibody–drug conjugates: Lessons learned from 40 years of development. Cancer Discov 2024;14(11):2089-108. Abstract

Herzog TJ et al. ARTISTRY-7: A phase 3, multicenter study of nemvaleukin alfa in combination with pembrolizumab versus chemotherapy in patients (pts) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. ASCO 2022;Abstract TPS5609.

Holloway RW et al. Phase 3 study of efficacy & safety of Olvi-Vec and platinum-doublet + bevacizumab compared to platinum-doublet + bevacizumab in platinum-resistant/refractory ovarian cancer (ONPRIME; GOG-3076). IGCS 2022;Abstract TPO26.

Holloway RW et al. Oncolytic vaccinia (olvi-vec) primed immunochemotherapy in platinum-resistant/refractory ovarian cancer. IGCS 2020;Abstract 1308.

Holloway RW et al. Phase II trial of oncolytic vaccinia virus primed immunochemotherapy in platinum-resistant/refractory ovarian cancer (PRROC) (NCT02759588). ESMO 2020;Abstract 837P.

Konecny G et al. Initial results of dose finding in a first-in-human phase 1 study of a novel Claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 in patients with advanced solid tumors. ASCO 2023;Abstract 3082.

Moore KN et al. Raludotatug deruxtecan (R-DXd; DS-6000) monotherapy in patients with previously treated ovarian cancer (OVC): Subgroup analysis of a first-in-human phase I study. ESMO 2023;Abstract 745MO.

Vaishampayan UN et al. Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1). J Immunother Cancer 2024;12(11):e010143. Abstract

Wang D et al. Safety and efficacy of sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced endometrial carcinoma (EC) and ovarian cancer (OC) from a phase II study. ESMO 2024;Abstract 715MO.

 

Dr Salani

Berek JS et al. Safety and dose modification for patients receiving niraparib. Ann Oncol 2018;29(8):1784-92. Abstract

González-Martin A et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019;381(25):2391-402. Abstract

Ledermann JA et al. Overall survival (OS) in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy: An interim analysis. ASCO 2016;Abstract 5501.

Moore KN et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med 2023;389(23):2162-74. Abstract

Moore KN et al. Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator’s choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. ASCO 2023;Abstract LBA5507.

Moore KN et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379(26):2495-505. Abstract

Ray-Coquard I et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. N Engl J Med 2019;381:2416-28. Abstract

Faculty

TARGET AUDIENCE
This activity is intended for gynecologic oncologists, medical oncologists, gynecologists and other healthcare providers involved in the treatment of gynecologic cancers.

LEARNING OBJECTIVES

• Appreciate the prevalence and relevance of HER2 amplification/overexpression in various gynecologic cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate published research findings with established HER2-targeted therapies for patients with HER2-positive gynecologic cancers, and assess the current role of various agents and regimens.
• Recall available data with novel HER2-targeted antibody-drug conjugates for HER2-positive ovarian, endometrial and cervical cancers, and optimally integrate these agents into the care of appropriately selected patients.
• Appraise the side effects associated with various HER2-directed therapies commonly employed in the care of patients with gynecologic cancers, and use this information to develop supportive therapeutic plans for those undergoing treatment with these agents or regimens.
• Recall the design of ongoing clinical trials evaluating novel HER2-directed agents and strategies for advanced HER2-positive gynecologic 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 to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
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 component and a post-test, 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, this program has 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, 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, this program has 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
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/SGO25HER2PosGyn/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:

Kathleen N Moore, MD, MS
Deputy Director
Virginia Kerley Cade Chair in Developmental Therapeutics
Co-Director, Cancer Therapeutics Program
Stephenson Cancer Center at the University of Oklahoma HSC
Associate Director, GOG Partners
Board of Directors, GOG Foundation
Board of Directors, ASCO
Oklahoma City, Oklahoma

Advisory Committees: Aadi Bioscience, AbbVie Inc, AstraZeneca Pharmaceuticals LP, BioNTech SE, Blueprint Medicines, Caris Life Sciences, Corcept Therapeutics, Daiichi Sankyo Inc, Duality Biologics, Eisai Inc, Genentech, a member of the Roche Group, GSK, ImmunoGen Inc, Janssen Biotech Inc, Lilly, Merck, Mersana Therapeutics Inc, Novartis, Regeneron Pharmaceuticals Inc, Schrödinger, Takeda Pharmaceuticals USA Inc, Verastem Inc, Zentalis Pharmaceuticals, Zymeworks Inc; Contracted Research: Allarity Therapeutics, Daiichi Sankyo Inc, GSK, ImmunoGen Inc, Schrödinger, Verastem Inc; Data and Safety Monitoring Boards/Committees: Bicycle Therapeutics.

Alessandro D Santin, MD
Professor
Department of Obstetrics and Gynecology
Co-Chief, Gynecologic Oncology
Yale University School of Medicine
New Haven, Connecticut

Advisory Committees: Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, Merck, Pfizer Inc, R-Pharm US; Contracted Research: Boehringer Ingelheim Pharmaceuticals Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Merck, R-Pharm US, Synthon, Tesaro, A GSK Company, Verastem Inc.

MODERATOR
David M O’Malley, MD
Director and Professor
Division of Gynecologic Oncology in Obstetrics and Gynecology
John G Boutselis Chair in Gynecologic Oncology
The Ohio State University and The James Comprehensive Cancer Center
Columbus, Ohio

Advisory Committees and Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Corcept Therapeutics, Duality Biologics, Genmab US Inc, GSK, Merck, MSD, Regeneron Pharmaceuticals Inc, Seagen Inc, Sumitomo Dainippon Pharma Oncology Inc, Sutro Biopharma, Verastem Inc; Contracted Research: AbbVie Inc, Adaptimmune, Advaxis Inc, Agenus Inc, Alkermes, Aravive Inc, Arcus Biosciences, Arquer Diagnostics, AstraZeneca Pharmaceuticals LP, Atossa Therapeutics, BeiGene Ltd, Bristol Myers Squibb, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals Inc, Duality Biologics, Eisai Inc, Elevar Therapeutics, EMD Serono Inc, Exelixis Inc, Genelux Corporation, Genentech, a member of the Roche Group, Genmab US Inc, GSK, ImmunoGen Inc, Imvax Inc, Incyte Corporation, InterVenn Biosciences, InxMed, Iovance Biotherapeutics, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Laekna Therapeutics, Leap Therapeutics Inc, Luzsana Biotechnology, Merck, Mersana Therapeutics Inc, MSD, Myriad Genetic Laboratories Inc, Novartis, Novocure Inc, Onconova Therapeutics Inc, OncoQuest Inc, Pfizer Inc, Predictive Oncology Inc, Prelude Therapeutics, Regeneron Pharmaceuticals Inc, Replimune, Roche Laboratories Inc, R-Pharm US, Rubius Therapeutics, Seagen Inc, Sorrento Therapeutics, Sumitomo Dainippon Pharma Oncology Inc, Sutro Biopharma, Tarveda Therapeutics, Tesaro, A GSK Company, Toray Industries Inc, Trillium Therapeutics Inc, Umoja Biopharma, VBL Therapeutics, Verastem Inc, Vincerx Pharma, Xencor, Zentalis Pharmaceuticals; Nonrelevant Financial Relationships: Amarex Clinical Research, GOG Foundation, Ludwig Institute for Cancer Research Ltd, National Cancer Institute, NRG Oncology, RTOG Foundation, SWOG.

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: April 2025
Expiration date: April 2026

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

Dr Santin

Black JD et al. PIK3CA oncogenic mutations represent a major mechanism of resistance to trastuzumab in HER2/neu overexpressing uterine serous carcinomas. Br J Cancer 2015;113(7):1020-6. Abstract

Buza N. HER2 testing in endometrial serous carcinoma: Time for standardized pathology practice to meet the clinical demand. Arch Pathol Lab Med 2021;145(6):687-91. Abstract

Cancer Genome Atlas Research Network. Integrated genomic and molecular characterization of cervical cancer. Nature 2017;543(7645):378-84. Abstract

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474(7353):609-15. Abstract

English DP et al. T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Med 2014;3(5):1256-65. Abstract

Levine DA et al. Integrated genomic characterization of endometrial carcinoma. Nature 2013;497(7447):67-73. Abstract

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

 

Dr O’Malley

Ahn ER et al. Pertuzumab plus trastuzumab in patients with endometrial cancer with ERBB2/3 amplification, overexpression, or mutation: Results from the TAPUR study. JCO Precis Oncol 2023:7. Abstract

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391(22):2110-22. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;LBA1000.

Fader AN et al. Randomized phase II trial of carboplatin-paclitaxel compared with carboplatin-paclitaxel-trastuzumab in advanced (stage III-IV) or recurrent uterine serous carcinomas that overexpress Her2/Neu (NCT01367002): Updated overall survival analysis. Clin Cancer Res 2020;26(15):3928-35. Abstract

Fader AN et al. Randomized phase II trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-trastuzumab in uterine serous carcinomas that overexpress human epidermal growth factor receptor 2/neu. J Clin Oncol 2018;36(20):2044-51. Abstract

Hasegawa K et al. Efficacy and safety of trastuzumab deruxtecan in HER2-expressing uterine carcinosarcoma (STATICE trial, NCCH1615): A multicenter, phase II clinical trial. ESMO 2021;Abstract 813P.

Jhaveri KL et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: Results from the NCI-MATCH trial (EAY131) subprotocol Q. Ann Oncol 2019;30(11):1821-30. Abstract

Lee J-Y et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Results from the cervical, endometrial, and ovarian cancer cohorts of the DESTINY-PanTumor02 study. International Gynecological Cancer Society 2023;Abstract 1550.

Makker V et al. Efficacy and safety of trastuzumab deruxtecan among patients with HER2-expressing solid tumors: Biomarker and subgroup analyses from the cervical, endometrial, and ovarian cancer cohorts of the DESTINY-PanTumor02 study. SGO 2024;Abstract 04.

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study. ESMO 2023;Abstract 376O.

Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387(1):9-20. Abstract

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. ASCO 2022;Abstract LBA3.

Moore K et al. DB-1303, a HER2-targeting ADC, for patients with advanced/metastatic endometrial cancer: Preliminary clinical results from an ongoing phase 1/2a trial (NCT05150691). ESGO 2023;Abstract 430.

Nakamura Y et al. Tucatinib and trastuzumab for previously treated human epidermal growth factor receptor 2-positive metastatic biliary tract cancer (SGNTUC-019): A phase II basket study. J Clin Oncol 2023;41(36):5569-78. Abstract

Nishikawa T et al. Trastuzumab deruxtecan for human epidermal growth factor receptor 2-expressing advanced or recurrent uterine carcinosarcoma (NCCH1615): The STATICE trial. J Clin Oncol 2023;41(15):2789-99. Abstract

Okines AFC et al. Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: A phase 2 basket trial. Nat Med 2025;31(3):909-16. Abstract

 

Dr Moore

Abelman RO et al. Association of pretreatment chest CT abnormalities with trastuzumab deruxtecan–associated pneumonitis. ASCO 2023;Abstract 1106.

Nguyen TD et al. Mechanisms of ADC toxicity and strategies to increase ADC tolerability. Cancers (Basel) 2023;15(3):713. Abstract

Pedersini R et al. Gastrointestinal toxicity of antibody drug conjugates (ADCs) in metastatic breast cancer: A pooled analysis. Clin Breast Cancer 2024;24(5):411-20. Abstract

Rugo H et al. Pooled analysis of trastuzumab deruxtecan (T-DXd) retreatment (RTx) after recovery from grade (Gr) 1 interstitial lung disease/pneumonitis (ILD). ESMO Breast Cancer 2024;Abstract 267MO.

Rugo H et al. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open 2022;7(4). Abstract

Swain SM et al. Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-focus on proactive monitoring, diagnosis, and management. Cancer Treat Rev 2022;106:102378. Abstract

Tarantino P, Tolaney SM. Detecting and managing T-DXd-related interstitial lung disease: The five “S” rules. JCO Oncol Pract 2023;19(8):526-27. Abstract

Zhu Y et al. Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis. Cancer 2023;129(2):283-95. Abstract

Faculty

TARGET AUDIENCE
This program is intended for medical and radiation oncologists, urologists and other healthcare providers involved in the treatment of bladder and prostate cancers.

LEARNING OBJECTIVES

• Recognize the incidence of nectin-4 expression in urothelial bladder cancer (UBC), and appreciate the scientific justification for the development of antibody-drug conjugates (ADCs) targeting this novel biomarker.
• Interrogate published efficacy and safety findings with anti-PD-1/PD-L1 antibodies in combination with ADC therapy as first-line treatment for metastatic UBC, and consider the current role of this strategy.
• Review available research findings with HER2-directed ADCs for patients with advanced UBC, and optimally integrate these novel agents into management algorithms.
• Appraise published research on the optimal management of biochemical recurrence after local treatment for prostate cancer, and counsel appropriate patients about the potential benefits of FDA-approved systemic treatment options.
• Explore available data with treatment intensification with cytotoxic therapy, secondary hormonal therapy or combinations of these approaches for metastatic hormone-sensitive prostate cancer, and effectively integrate these strategies into clinical management algorithms.
• Assess the available research database supporting the use of PARP inhibitors in combination with androgen receptor pathway inhibitors for patients with metastatic castration-resistant prostate cancer harboring a homologous recombination repair gene alteration, and discern the current role of this treatment approach.
• Recall the design of ongoing clinical trials evaluating novel ADCs for advanced UBC or hormonal therapy-based approaches for prostate cancer, and counsel appropriate patients about availability and 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
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)
CME credit is no longer available for this issue

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS 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.
CME credit is no longer available for this issue

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:

Neeraj Agarwal, MD, FASCO
Professor of Medicine
Senior Director for Clinical Research
Huntsman Cancer Institute Presidential Endowed Chair of Cancer Research
Director, Center of Investigational Therapeutics
Director, Genitourinary Oncology Program
Huntsman Cancer Institute, University of Utah (NCI-CCC)
Salt Lake City, Utah

No relevant conflicts of interest to disclose.

Andrew J Armstrong, MD, ScM
Professor of Medicine, Surgery, Pharmacology and Cancer Biology
Director of Research
Duke Cancer Institute Center for Prostate and Urologic Cancers
Divisions of Medical Oncology and Urology
Duke University
Durham, North Carolina

Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Cytogen Corporation, Janssen Biotech Inc, Merck, Myovant Sciences, Novartis, Pfizer Inc; Consulting Agreements: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Curium, Janssen Biotech Inc, Merck, Novartis, Pfizer Inc; Contracted Research: Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Janssen Biotech Inc, Merck, Novartis, Pathos, Pfizer Inc.

Terence Friedlander, MD
Professor of Medicine and Robert and Virginia O’Reilly Family Endowed Chair
Chief, Division of Hematology/Oncology
Zuckerberg San Francisco General Hospital
Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
San Francisco, California

Advisory Committees: Aadi Bioscience, AbbVie Inc, Adaptimmune, Aktis Oncology, Astellas, Bicycle Therapeutics, Bristol Myers Squibb, Gilead Sciences Inc, Merck, Pfizer Inc, Samsung Bioepis; Consulting Agreements: Astellas, EMD Serono Inc, Pfizer Inc; Contracted Research: Bicycle Therapeutics, Genentech, a member of the Roche Group, Johnson & Johnson Pharmaceuticals, Pfizer Inc; Data and Safety Monitoring Boards/Committees: Bicycle Therapeutics.

Matthew D Galsky, MD
Professor of Medicine
Icahn School of Medicine at Mount Sinai
Co-Leader, Bladder Cancer Center of Excellence
Associate Director, Translational Research
The Tisch Cancer Institute
New York, New York

Advisory Committees: AbbVie Inc, Aktis Oncology, Alligator Bioscience, Analog Devices Inc, Asieris Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Basilea Pharmaceutica Ltd, Bicycle Therapeutics, Bristol Myers Squibb, Curis Inc, Daiichi Sankyo Inc, Dragonfly Therapeutics, EMD Serono Inc, FUJIFILM Pharmaceuticals USA Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Janssen Biotech Inc, Merck, Numab Therapeutics AG, Pfizer Inc, Rappta Therapeutics, Seagen Inc, Silverback Therapeutics, UroGen Pharma, Veracyte Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Dendreon Pharmaceuticals Inc, Genentech, a member of the Roche Group, Merck, Novartis.

MODERATOR
Elisabeth I Heath, MD
Chair, Department of Oncology
Mayo Clinic
Rochester, Minnesota

Advisory/Consulting: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Sanofi; Honoraria/Paid Travel: Astellas, Bayer HealthCare Pharmaceuticals, Caris Life Sciences, Sanofi, Seagen Inc; Institutional Research Support: Amgen Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BioXcel Therapeutics Inc, Bristol Myers Squibb, Calithera Biosciences, Caris Life Sciences, Corcept Therapeutics, Corvus Pharmaceuticals, Daiichi Sankyo Inc, Eisai Inc, Exelixis Inc, F Hoffman-La Roche Ltd, Fortis Therapeutics, Gilead Sciences Inc, GSK, Harpoon Therapeutics, Infinity Pharmaceuticals Inc, iTeos Therapeutics, Janssen Biotech Inc, Merck, Mirati Therapeutics Inc, Modra Pharmaceuticals, MSD, Novartis, Oncolys BioPharma, Peloton Therapeutics Inc, a wholly-owned subsidiary of Merck & Co Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, POINT Biopharma, Seagen Inc; Steering Committees: Janssen Biotech Inc; Speakers Bureaus: Sanofi; Nonrelevant Financial Relationships: Calibr-Skaggs Institute for Innovative Medicines.

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 grantor.

These activities are supported by an educational grant from Astellas and Pfizer Inc.

Release date: March 2025
Expiration date: March 2026

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

Urothelial Bladder Cancer

Dr Friedlander

O’Donnell PH et al. Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer. J Clin Oncol. 2023 Sep 1;41(25):4107-17. Abstract

Powles T et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). Genitourinary Cancers Symposium 2025;Abstract 664.

Powles T et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med 2024;390(10):875-88. Abstract

Powles T et al. EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). ESMO 2023;Abstract LBA6.

Powles T et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 2021;384(12):1125-35. Abstract

Rosenberg JE et al. Long-term outcomes in EV-301: 24-month findings from the phase 3 trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. ASCO 2022;Abstract 4516.

Rosenberg JE et al. Study EV-103 cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC). ESMO 2022;Abstract LBA73.

 

Dr Galsky

Aggen DH et al. HER2 and PD-L1 immunohistochemistry (IHC) expression, and HER2 genomic alterations: Associations and clinical outcomes for advanced bladder cancer. Genitourinary Cancers Symposium 2024;Abstract 538.

Galsky MD et al. Preliminary efficacy and safety of disitamab vedotin (DV) with pembrolizumab (P) in treatment (Tx)-naive HER2-expressing, locally advanced or metastatic urothelial carcinoma (la/mUC): RC48G001 cohort C. ESMO 2024;Abstract 1967MO.

Galsky MD et al. Phase 2 multi-cohort clinical study evaluating disitamab vedotin alone and in combination with pembrolizumab in patients with HER2-expressing unresectable or metastatic urothelial carcinoma (RC48G001, trial in progress). SITC 2022;Abstract 663.

Galsky MD et al. Primary analysis from DS8201-A-U105: A phase 1b, 2-part, open-label study of trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing urothelial carcinoma (UC). Genitourinary Cancers Symposium 2022;Abstract 438.

Grivas P et al. Sacituzumab govitecan in combination with pembrolizumab for patients with metastatic urothelial cancer that progressed after platinum-based chemotherapy: TROPHY-U-01 cohort 3. J Clin Oncol 2024;42(12):1415-25. Abstract

Hamilton E et al. Trastuzumab deruxtecan with nivolumab in HER2-expressing metastatic breast or urothelial cancer: Analysis of the phase Ib DS8201-A-U105 study. Clin Cancer Res. 2024;30(24):5548-58. Abstract

Li BT et al. Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): An international, phase 2 study. Lancet Oncol 2024;25(6):707-19. Abstract

Li BT et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with solid tumors harboring specific HER2-activating mutations (HER2m): Primary results from the international phase II DESTINY-PanTumor01 (DPT-01) study. ESMO 2023;Abstract 654O.

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

Meric-Bernstam F et al. Trastuzumab deruxtecan (T-DXd) for pretreated patients (pts) with HER2-expressing solid tumors: Primary analysis from the DESTINY-PanTumor02 (DP-02) study. ESMO 2023;Abstract LBA34.

O’Donnell PH et al. Enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial cancer. J Clin Oncol 2023;41(25):4107-17. Abstract

Rosenberg JE et al. EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma. Ann Oncol 2023;34(11):1047-54. Abstract

Sheng X et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma: A Combined analysis of two phase II clinical trials. J Clin Oncol 2024;42(12):1391-402. Abstract

Sheng X et al. RC48-ADC for metastatic urothelial carcinoma with HER2-positive: Combined analysis of RC48-C005 and RC48-C009 trials. ASCO 2022;Abstract 4520.

Xu H et al. A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. ASCO 2022;Abstract 4519.

Zhou L et al. Disitamab vedotin (DV) plus toripalimab (T) in unresectable locally advanced or metastatic urothelial carcinoma (la/mUC): Long-term outcomes from a phase Ib/II study. ESMO 2024;Abstract 1979P.

 

Prostate Cancer

Dr Armstrong

Armstrong AJ et al. The efficacy of enzalutamide plus androgen deprivation therapy in oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. Eur Urol 2023;84(2):229-41. Abstract

Armstrong AJ et al. Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol 2022;40(15):1616-22. Abstract

Attard G et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: A meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet 2022;399(10323):447-60. Abstract

Attard G et al. Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol. ESMO 2022;Abstract LBA62.

Freedland SJ et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med 2023;389(16):1453-65. Abstract

Hussain M et al. Darolutamide plus androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer by disease volume and risk subgroups in the phase III ARASENS trial. J Clin Oncol 2023;41(20):3595-607. Abstract

McManus HD, Armstrong AJ. The past, present, and future of treatment intensification for metastatic hormone-sensitive prostate cancer. J Clin Oncol 2023;41(20):3576-9. Abstract

Merseburger AS et al. Targeted investigational treatment analysis of novel anti-androgen (TITAN) study: Ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy. BJU Int 2024;134(6):982-91. Abstract

Smith MR et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 2022;386(12):1132-42. Abstract

Smith MR et al. Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial. Genitourinary Cancers Symposium 2022;Abstract 13.

Sweeney CJ et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015;373(8):737-46. Abstract

Tang C et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer: The EXTEND phase 2 randomized clinical trial. JAMA Oncol 2023;9(6):825-34. Abstract

 

Dr Agarwal

Agarwal N et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. Genitourinary Cancers Symposium 2025;Abstract LBA18.

Agarwal N et al. EvoPAR-Prostate01: Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with new hormonal agents in patients with mCSPC +/- HRR mutations. AUA 2024.

Agarwal N et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomised, placebo-controlled, phase 3 trial. Lancet 2023;402(10398):291-303. Abstract

Agarwal N et al. Talapro-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) versus placebo plus enza in patients with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC). Genitourinary Cancers Symposium 2022;Abstract TPS 221.

Chi KN et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Oncol 2023;41(18):3339-51. Abstract

Chi KN et al. Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Three-year update and final analysis (FA) of MAGNITUDE. ESMO 2023;Abstract LBA85.

Chi KN et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: Second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol 2023;34(9):772-82. Abstract

Chi KN et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Genitourinary Cancers Symposium 2022;Abstract 12.

Clarke NW et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid 2022;1(9). Abstract

Fizazi K et al. First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: The phase 3 TALAPRO-2 trial. Nat Med 2024;30(1):257-64. Abstract

Hussain M et al. BRCAAway: A randomized phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) bearing homologous recombination-repair mutations (HRRm). Genitourinary Cancers Symposium 2024;Abstract 19.

Rathkopf DE et al. AMPLITUDE: A study of niraparib in combination with abiraterone acetate plus prednisone (AAP) versus AAP for the treatment of patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC). Genitourinary Cancers Symposium 2021;Abstract TPS176.

Saad F et al. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): Final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(10):1094-108. Abstract

Swami U et al. Treatment pattern and outcomes with systemic therapy in men with metastatic prostate cancer in the real-world patients in the United States. Cancers (Basel) 2021;13(19):4951. Abstract

Faculty

TARGET AUDIENCE
This program is intended for medical and radiation oncologists, urologists and other healthcare providers involved in the treatment of renal cell carcinoma.

LEARNING OBJECTIVES

• Evaluate recently presented data with adjuvant anti-PD-1/PD-L1 antibody therapy for patients with RCC at high risk for recurrence after nephrectomy, and consider the current role of this treatment strategy.
• Appraise available clinical trial data evaluating anti-PD-1/PD-L1 antibody/multikinase inhibitor combinations for previously untreated metastatic RCC (mRCC), and counsel patients regarding the risks and benefits of these novel regimens.
• Review the biological rationale underlying the investigation of anti-PD-1/anti-CTLA-4 combination therapy as first-line treatment for patients with mRCC, and appreciate long-term research findings documenting the effectiveness of this approach.
• Assess recently presented clinical trial results with anti-PD-1/PD-L1 antibodies administered as a subcutaneous injection for patients with mRCC, and reflect on the potential benefits of this therapeutic strategy.
• Understand the biological rationale for exploiting HIF-2α in patients with von Hippel-Lindau-associated and sporadic RCC, and consider the current role of available inhibitors.
• Develop a rational therapeutic approach to the sequencing of systemic therapies for patients with advanced RCC that progresses on first-line treatment, incorporating multikinase inhibitors, HIF-2α inhibitors, immunotherapeutic agents and other strategies.
• Appreciate published research findings evaluating the use of available and investigational agents for patients with non-clear cell RCC, and consider the applicability of these strategies in clinical care.
• Recall available and emerging data with other novel and investigational agents and strategies in testing for RCC, and as applicable, refer eligible patients for clinical trial 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) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and a short 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 an video component.
CME credit is no longer available for this issue

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:

Thomas E Hutson, DO, PharmD, PhD
Director
UMC Cancer Center
Division Chief, Hematology and Medical Oncology
Professor of Medicine
CH Endowed Chair
Texas Tech University Health Sciences Center School of Medicine
Lubbock, Texas

Advisory Committees, Consulting Agreements, Contracted Research and Speakers Bureaus: Astellas, AstraZeneca Pharmaceuticals LP, EMD Serono Inc, Exelixis Inc, Merck, Pfizer Inc, Seagen Inc.

Rana R McKay, MD
Professor of Medicine and Urology
Associate Director, Clinical Research
Co-Lead, Genitourinary Program
Moores Cancer Center
University of California San Diego
San Diego, California

Advisor/Consultant: Ambrx, Arcus Biosciences, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Blue Earth Diagnostics, Bristol Myers Squibb, Calithera Biosciences, Caris Life Sciences, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Exelixis Inc, Johnson & Johnson Pharmaceuticals, Lilly, Merck, Myovant Sciences, Neomorph, Novartis, Pfizer Inc, Sanofi, Seagen Inc, Sorrento Therapeutics, Telix Pharmaceuticals Limited, Tempus; Institutional Research Funding: ArteraAI, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Exelixis Inc, Oncternal Therapeutics, Tempus.

Tian Zhang, MD, MHS
Associate Professor
Director of Clinical Research
Division of Hematology and Oncology
Department of Internal Medicine
UT Southwestern Medical Center
Associate Director for Clinical Research
Simmons Comprehensive Cancer Center
Dallas, Texas

Advisory Committees: Amgen Inc, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, Gilead Sciences Inc, Janssen Biotech Inc, Lilly, Merck, Novartis, Pfizer Inc, Sanofi; Consulting Agreements: Aptitude Health, DAVA Oncology, Pfizer Inc, Vaniam Group; Contracted Research: ALX Oncology, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Exelixis Inc, Janssen Biotech Inc, Janux Therapeutics, Lilly, Merck, OncoC4, Pfizer Inc, Tempus; Nonrelevant Financial Relationships: Mashup Media LLC, MJH Life Sciences, PeerView.

MODERATOR
Sumanta Kumar Pal, MD
Professor and Vice Chair of Academic Affairs
Department of Medical Oncology
City of Hope Comprehensive Cancer Center
Duarte, California

Travel Support: CRISPR Therapeutics, EverImmune, Exelixis Inc, Ipsen Biopharmaceuticals Inc.

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 Bristol Myers Squibb, Eisai Inc, and Exelixis Inc.

Release date: March 2025
Expiration date: March 2026

Dr Hutson

Albiges L et al. Cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC): Final results of COSMIC-313. Genitourinary Cancers Symposium 2025;Abstract 438.

Bourlon MT et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). Genitourinary Cancers Symposium 2024;Abstract 362.

Choueiri TK et al. Overall survival results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab versus placebo for the treatment of clear cell renal cell carcinoma (ccRCC). ASCO 2024;Abstract LBA359.

Choueiri TK et al. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med 2024;390(15):1359-71. Abstract

George S et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. Genitourinary Cancers Symposium 2024;Abstract LBA360.

Grünwald V et al. Analyses on impact of tumor burden at progression and changes in IMDC from baseline in patients (pts) with advanced renal cell carcinoma (aRCC) treated with lenvatinib + pembrolizumab (L+P) in the phase 3 CLEAR trial. Genitourinary Cancers Symposium 2025;Abstract 531.

Motzer RJ et al. Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate 9ER trial. Genitourinary Cancers Symposium 2025;Abstract 439.

Motzer RJ et al. Lenvatinib plus pembrolizumab versus sunitinib in first-line treatment of advanced renal cell carcinoma: Final prespecified overall survival analysis of CLEAR, a phase III study. J Clin Oncol 2024;42(11):1222-8. Abstract

Motzer RJ et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). ASCO 2023;Abstract 4502.

Powles T et al. Outcomes by IMDC risk in the COSMIC-313 phase 3 trial evaluating cabozantinib (C) plus nivolumab (N) and ipilimumab (I) in first-line advanced RCC (aRCC) of IMDC intermediate or poor risk. Genitourinary Cancers Symposium 2023;Abstract 605.

Rini BI et al. Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma: 5-year analysis of KEYNOTE-426. ASCO 2023;Abstract LBA4501.

Tannir NM et al. Nivolumab plus ipilimumab (NIVO+IPI) vs sunitinib (SUN) for first-line treatment of advanced renal cell carcinoma (aRCC): Long-term follow-up data from the phase 3 CheckMate 214 trial. Genitourinary Cancers Symposium 2024;Abstract 363.

 

Dr Zhang

Braun DA et al. Beyond conventional immune-checkpoint inhibition — Novel immunotherapies for renal cell carcinoma. Nat Rev Clin Oncol 2021;18(4):199-214. Abstract

Choueiri TK et al. Tivozanib–nivolumab vs tivozanib monotherapy in patients with renal cell carcinoma (RCC) following 1 or 2 prior therapies including an immune checkpoint inhibitor (ICI): Results of the phase III TiNivo-2 study. ESMO 2024;Abstract LBA73.

Pal SK et al. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): A multicentre, randomised, open-label, phase 3 trial. Lancet 2023;402(10397):185-95. Abstract

Rini BI et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): A phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol 2020;21(1):95-104. Abstract

Zhu S et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol 2021;14(1):156. Abstract

 

Dr McKay

Agarwal N et al. Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma. Ann Oncol 2024;35(12):1148-56. Abstract

Albiges L et al. KEYMAKER-U03 Substudy 03B: Pembrolizumab (pembro) and targeted therapy combinations for advanced clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2025;Abstract 440.

Barata P et al. Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles. J Clin Invest 2024;134(11):e178915. Abstract

Choueiri TK et al. Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): An open-label, single-arm, phase 2 study. Lancet Oncol 2025;26(1):64-73. Abstract

Choueiri TK et al. Casdatifan (Cas) monotherapy in patients (pts) with previously treated clear cell renal cell carcinoma (ccRCC): Safety, efficacy and subgroup analysis across multiple doses from ARC-20, a phase 1 open-label study. Genitourinary Cancers Symposium 2025;Abstract 441.

Choueiri TK et al. Updated results from the phase 2 LITESPARK-003 study of belzutifan plus cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2025;Abstract 549.

Choueiri TK et al. Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC- 20: A phase 1, open-label dose-escalation and expansion study. EOORTC-NCI-AACR Symposium 2024;Abstract 4 Oral.

Choueiri TK et al. Safety profile of belzutifan monotherapy in patients with renal cell carcinoma: A pooled analysis of 4 clinical trials. KCRS 2024;Abstract 39.

Choueiri TK et al. LITESPARK-012: Pembrolizumab plus lenvatinib with or without belzutifan or quavonlimab for advanced renal cell carcinoma. Future Oncol 2023;19(40):2631-40. Abstract

Choueiri TK et al. Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC). Genitourinary Cancers Symposium 2023;Abstract TPS748.

Choueiri TK et al. Phase II LITESPARK-003 study of belzutifan in combination with cabozantinib for advanced clear cell renal cell carcinoma (ccRCC). ESMO 2023;Abstract LBA87.

de Velasco G et al. Efficacy outcomes with belzutifan versus everolimus by baseline disease characteristics and burden subgroups in the phase 3 LITESPARK-005 study. Genitourinary Cancers Symposium 2025;Abstract 538.

Jonasch E et al. NKT2152, a novel oral HIF-2α inhibitor, in participants (pts) with previously treated advanced clear cell renal carcinoma (accRCC): Preliminary results of a phase I/II study. ESMO 2024;Abstract 16900.

Jonasch E et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med 2021;385(22):2036-46. Abstract

Motzer RJ et al. LITESPARK-011: Belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Future Oncol 2023;19(2):113-21. Abstract

Pezzicoli G et al. Genomic profiling and molecular characterization of clear cell renal cell carcinoma. Curr Oncol 2023;30(10):9276-90. Abstract

Rini BI et al. Final analysis of the phase III LITESPARK-005 study of belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC). ESMO 2024;Abstract LBA74.

 

Dr Pal

Albiges L et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): A single-arm, multicentre, phase 2 trial. Lancet Oncol 2023;24(8):881-91. Abstract

Alhalabi O et al. Immune checkpoint therapy combinations in adult advanced MiT family translocation renal cell carcinomas. Oncologist 2023;28(5):433-9. Abstract

Bakouny Z et al. Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Rep 2022;38(1):110190. Abstract

Barata P et al. Final overall survival analysis of S1500: A randomized, phase II study comparing sunitinib with cabozantinib, crizotinib, and savolitinib in advanced papillary renal cell carcinoma. J Clin Oncol 2024;42(33):3911-6. Abstract

Fitzgerald KN et al. Cabozantinib plus nivolumab in patients with non-clear cell renal cell carcinoma: Updated results from a phase 2 trial. Eur Urol 2024;86(2):90-4. Abstract

Hutson TE et al. A single-arm, multicenter, phase 2 study of lenvatinib plus everolimus in patients with advanced non-clear cell renal cell carcinoma. Eur Urol 2021;80(2):162-70. Abstract

McGregor BA et al. Results of a multicenter phase II study of atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma with variant histology and/or sarcomatoid features. J Clin Oncol 2020;38(1):63-70. Abstract

Montenegro GLB et al. A phase 2 study of bevacizumab, erlotinib, and atezolizumab in subjects with advanced hereditary leiomyomatosis and renal cell cancer (HLRCC) associated or sporadic papillary renal cell cancer (pRCC). ASCO 2022;Abstract 5004.

Naik P et al. The incidence, pathogenesis, and management of non-clear cell renal cell carcinoma. Ther Adv Urol 2024:16. Abstract

Pal SK et al. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: A randomised, open-label, phase 2 trial. Lancet 2021;397(10275):695-703. Abstract

Pal SK et al. Cabozantinib in combination with atezolizumab for advanced renal cell carcinoma: Results from the COSMIC-021 study. J Clin Oncol 2021;39(33):3725-36. Abstract

Procopio G et al. Cabozantinib as first-line treatment in patients with metastatic collecting duct renal cell carcinoma: Results of the BONSAI trial for the Italian Network for Research in Urologic-Oncology (Meet-URO 2 Study). JAMA Oncol 2022;8(6):910-3. Abstract

Salgia NJ et al. Renal cell carcinoma of variant histology: New biologic understanding leads to therapeutic advances. Am Soc Clin Oncol Educ Book 2024;44(3):e438642. Abstract

Sharma MR et al. A phase I first-in-human study of XL092 in patients (pts) with locally advanced or metastatic solid tumors: Results from dose-escalation of XL092 alone and in combination with atezolizumab. ESMO 2022;Abstract 481P.

Suarez C et al. Phase II study investigating the safety and efficacy of savolitinib and durvalumab in metastatic papillary renal cancer (CALYPSO). J Clin Oncol 2023;41(14):2493-502. Abstract

Voss MH et al. First-line pembrolizumab plus lenvatinib for non–clear cell renal carcinomas (nccRCC): Extended follow-up of the phase 2 KEYNOTE-B61 study. Genitourinary Cancers Symposium 2024;Abstract 2.

Wiele AJ et al. Efficacy and safety of bevacizumab plus erlotinib in patients with renal medullary carcinoma. Cancers (Basel) 2021;13(9):2170. Abstract

Wilson NR et al. Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma. Clin Genitourin Cancer 2021;19(6):e401-8. 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