Consensus or Controversy? Documenting and Discussing Investigators’ Approaches to the Management of Colorectal Cancer — Symposium Proceedings

Faculty

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

LEARNING OBJECTIVES

• Understand validated biomarkers of response (eg, RAS mutations, microsatellite instability [MSI]/mismatch repair [MMR] deficiency, HER2 overexpression, BRAF V600E mutations, KRAS G12C mutations) found in patients with CRC, and consider the implications for molecular testing and clinical care.
• Evaluate the biological rationale for the use of immune checkpoint inhibitors in the management of MSI-high (MSI-H)/MMR-deficient (dMMR) localized and advanced CRC, and counsel patients regarding evidence-based and guideline-endorsed treatment recommendations.
• Optimize the current and future use of neoadjuvant and adjuvant therapy for patients with localized and locally advanced CRC, considering the influence of various clinical and biological factors such as MSI-H/dMMR status.
• Recognize the clinical relevance of circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker in CRC, and comprehend the rationale for its use in detecting molecular residual disease.
• Appreciate published datasets documenting the clinical utility of ctDNA testing in risk stratification, surveillance and treatment decision-making for patients with CRC, and consider the current and future role of this strategy in personalizing therapeutic recommendations.
• Formulate a plan to guide the selection and sequencing of therapies for patients diagnosed with metastatic CRC (mCRC) accounting for tumor sidedness, biomarker profile, prior systemic therapy, symptomatology and personal goals of treatment.
• Appreciate published research documenting the efficacy of targeted therapeutic approaches for patients with mCRC and various actionable genomic alterations in order to personalize treatment recommendations.
• Recall ongoing trials evaluating novel agents and strategies for patients with mCRC, and use this information to refer candidates for study participation.

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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.

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Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.75 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 the 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) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, 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.

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HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, 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.

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

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

Andrea Cercek, MD (PowerPoint Slides) — Advisory Boards: 3T Biosciences, AbbVie Inc, Agenus Inc, Amgen Inc, Daiichi Sankyo Inc, GSK, Janssen Biotech Inc, Merck, Pfizer Inc, Regeneron Pharmaceuticals Inc, Roche Laboratories Inc, Summit Therapeutics, UroGen Pharma; Contracted Research: GSK, Pfizer Inc. Dr Cohen — Advisory Committees: AbbVie Inc, Blueprint Medicines, Boston Scientific Corporation, Caris Life Sciences, DoMore Diagnostics, Exact Sciences Corporation, Incyte Corporation, Janssen Biotech Inc, Merck, Pfizer Inc, Roche Laboratories Inc; Data and Safety Monitoring Boards/Committees: GSK. Dr Dasari — Advisory Committees: Agenus Inc, Bristol Myers Squibb, Exelixis Inc, Illumina, Lantheus, Personalis, Sanofi, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Bristol Myers Squibb, Crinetics Pharmaceuticals, Eisai Inc, Enterome, Guardant Health, Hutchison MediPharma, Natera Inc, NeoGenomics, Personalis, RayzeBio, Taiho Oncology Inc, Xencor.

CONTRIBUTING CLINICAL INVESTIGATORS
Marwan Fakih, MD — Advisory Committees: Genentech, a member of the Roche Group, Janssen Research and Development, Merus, Mirati Therapeutics Inc, Tempus, Xilio Therapeutics; Consulting Agreements: AbbVie Inc, Adagene, Bristol Myers Squibb, Delcath Systems Inc, Iterion Therapeutics, Merck, Microbial Machines, Mirati Therapeutics Inc, Revolution Medicines, Summit Therapeutics, Taiho Oncology Inc, Totus Medicines; Contracted Research: Agenus Inc. Christopher Lieu, MD — Consulting Agreements: Pfizer Inc; Contracted Research: Genentech, a member of the Roche Group, Janssen Biotech Inc. Anwaar Saeed, MD — Advisory Committees and Consulting Agreements: Amgen Inc, AstraZeneca Pharmaceuticals LP, Autem Therapeutics, BeOne, Bristol Myers Squibb, Exact Sciences Corporation, Exelixis Inc, KAHR Medical, Merck, Pfizer Inc, Regeneron Pharmaceuticals Inc, Replimune, Taiho Oncology Inc, Xilio Therapeutics; Contracted Research: Actuate Therapeutics, Arcus Biosciences, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Coherus BioSciences, Exelixis Inc, Henlius, Incyte Corporation, KAHR Medical, Merck, Oxford BioTherapeutics, Phanes Therapeutics Inc, Regeneron Pharmaceuticals Inc, Replimune; Data and Safety Monitoring Boards/Committees: Arcus Biosciences.

MODERATOR — Dr Bekaii-Saab — Consulting Agreements (to Institution): Arcus Biosciences, Bayer HealthCare Pharmaceuticals, Eisai Inc, Genentech, a member of the Roche Group, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Merck, Merck KGaA, Merus, Pfizer Inc, Revolution Medicines Inc, Seagen Inc, Servier Pharmaceuticals LLC; Consulting Agreements (to Self): AbbVie Inc, Aptitude Health, Arsenal Biosciences Inc, AstraZeneca Pharmaceuticals LP, BeOne, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Celularity, Daiichi Sankyo Inc, Deciphera Pharmaceuticals Inc, Exact Sciences Corporation, Exelixis Inc, Foundation Medicine, GSK, Illumina, Janssen Biotech Inc, Kanaph Therapeutics, Lisata Therapeutics, Natera Inc, Ryght AI, Sanofi, Sobi, Stemline Therapeutics Inc, Takeda Pharmaceuticals USA Inc, Treos Bio, Xilio Therapeutics, Zai Lab; Data and Safety Monitoring Boards/Committees: 1Globe Health Institute, AstraZeneca Pharmaceuticals LP, Eisai Inc, Exelixis Inc, FibroGen Inc, Merck, Suzhou Kintor; Inventions/Patents: WO/2018/183488 — Human PD-1 peptide vaccines and uses thereof, licensed to Imugene, WO/2019/055687 — Methods and compositions for the treatment of cancer cachexia, licensed to Recursion; Research Funding (to Institution): Agios Pharmaceuticals Inc, AltruBio, Arcus Biosciences, Arrys Therapeutics, a wholly owned subsidiary of Kyn Therapeutics, Atreca, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Celgene Corporation, Eisai Inc, Genentech, a member of the Roche Group, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Lilly, Merus, Mirati Therapeutics Inc, Novartis, Pfizer Inc, pharmaand GmbH, Revolution Medicines Inc, Seagen Inc, Sumitomo Pharma America; Scientific Advisory Boards: Artiva Biotherapeutics Inc, Immuneering Corporation, Imugene, Replimune, Xilis; Nonrelevant Financial Relationships: MJH Life Sciences, Pancreatic Cancer Action Network, The Valley Hospital, UpToDate.

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

This educational activity contains 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.

This activity is supported by educational grants from Exelixis Inc, GSK, and Natera Inc.

Release date: July 2026
Expiration date: July 2027

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

Dr Cohen

Cercek A et al. Nonoperative management of mismatch repair-deficient tumors. N Engl J Med 2025;392(23):2297-308. Abstract

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

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

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

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

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

Rousseau B et al. The duration of immunotherapy for mismatch repair-deficient cancers. N Engl J Med 2025;392(8):824-6. Abstract

Sinicrope FA et al. Atezolizumab plus FOLFOX for Stage III mismatch repair-deficient colon cancer. N Engl J Med 2026;394(12):1155-66. Abstract

Dr Dasari

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

Dasari A et al. Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA): NRG-GI008. Gastrointestinal Cancer Symposium 2025;Abstract TPS3644.

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

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

Raghav KPS et al. A phase 2 randomized study comparing telisotuzumab adizutecan monotherapy with standard of care in patients with post-adjuvant circulating tumor DNA-positive colorectal cancer. Gastrointestinal Cancers Symposium 2026;Abstract TPS265.

Tie J et al. Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: The randomized phase 2/3 DYNAMIC-III trial. Nat Med 2025;31(12):4291-300. Abstract

Zhang GQ et al. Predictive role of circulating tumor DNA in stage III colon cancer treated with celecoxib: A post hoc analysis of the CALGB (Alliance)/SWOG 80702 phase 3 randomized clinical trial. JAMA Oncol 2026;12(2):149-58. Abstract

Dr Bekaii-Saab

Andre T et al. First results of nivolumab (NIVO) plus ipilimumab (IPI) vs NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. Gastrointestinal Cancers Symposium 2025;Abstract LBA143.

Elez E et al. Encorafenib, cetuximab, and mFOLFOX6 in BRAF-mutated colorectal cancer. N Engl J Med 2025;392(24):2425-37. Abstract

Elez E et al. First-line encorafenib + cetuximab + mFOLFOX6 in BRAF V600E-mutant metastatic colorectal cancer (BREAKWATER): Progression-free survival and updated overall survival analyses. ASCO 2025;Abstract LBA3500.

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

Hecht JR et al. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): A randomised, open-label, phase 3 trial. Lancet 2025;406(10517):2360-70. Abstract

Kopetz S et al. BREAKWATER: Primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). Gastrointestinal Cancers Symposium 2026;Abstract 13.

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

Lonardi S et al. Nivolumab plus ipilimumab vs nivolumab monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): New results from CheckMate 8HW. ESMO 2025;Abstract LBA29.

Saeed A et al. STELLAR-303: Randomized phase III study of zanzalintinib + atezolizumab in previously treated metastatic colorectal cancer. Future Oncol 2024;20(24):1733-43. Abstract

Shiu K-K et al. KEYNOTE-177: Phase III randomized study of pembrolizumab versus chemotherapy for microsatellite instability-high advanced colorectal cancer. Gastrointestinal Cancers Symposium 2021;Abstract 6.