Updates from ASCO 2024: Colorectal Cancer

Educational Objectives

The goal of this program is to provide updates on the management of colorectal cancer. After hearing and assimilating this program, the clinician will be better able to:

1. Choose immunotherapy rather than chemotherapy for treatment of metastatic colorectal cancer.
2. Use circulating tumor DNA for the management of colon cancer.

Summary

Recurrent metastatic disease: CheckMate 8HW study (Andre et al [2024]) — randomized metastatic colorectal cancer (CRC) patients 2:2:1 to receive nivolumab (NIVO), NIVO plus ipilimumab (IPI), or chemotherapy, with crossover allowed from chemotherapy; so far, only results comparing NIVO-IPI vs chemotherapy have been presented; for patients with microsatellite instability (MSI)-high disease, NIVO-IPI showed significantly improved progression-free survival (PFS) compared with chemotherapy, and time to progression on second treatment (PFS2) confirmed this benefit; PFS2 is a better predictor of overall survival (OS) than PFS; subgroup analysis also favored NIVO-IPI across all metastasis sites (liver, lung, peritoneal); no new toxicity signals were identified, though there were 2 treatment-related deaths in the NIVO-IPI arm; findings align with National Comprehensive Cancer Network (NCCN) guidelines, which support immunotherapy over chemotherapy in MSI-high patients, with caution advised regarding the potential toxicity of the NIVO-IPI combination; SEAMARK study — ongoing; intensifying immunotherapy with encorafenib plus cetuximab in patients with dual mutations (MSI-high and BRAF V600E)

Locally advanced disease: NEOPRISM-CRC study — involved patients with MSI-high stage II or III CRC who had not yet undergone surgery; patients received one dose of pembrolizumab and were stratified by tumor mutation burden (TMB); after additional immunotherapy, patients proceeded to surgery, with the primary outcome being the pathologic complete response (pCR) rate; the intent-to-treat pCR rate was 53%, while the evaluable tumor pCR rate was 58%; however, 2 patients with high TMB did not respond, highlighting variability in response; toxicities were as expected, but bulky tumors increased the risk for complications; comparing neoadjuvant data for CRC — NEOPRISM evaluated pembrolizumab, NICHE-2 used NIVO-IPI, and NICHE-3 studied NIVO plus relatlimab; the Memorial Sloan Kettering Cancer Center study focused on dostarlimab for mismatch repair-deficient rectal cancer; AZUR-1 study is ongoing; NEST-1 included both MSI-high and microsatellite stability (MSS) tumors, with MSS tumors showing a 67% response to botensilimab plus balstilimab; EA2205 examined immunotherapy with short-course radiation in MSI-high rectal cancers, with data pending; the NCCN guidelines suggest that, for T4 or unresectable colon and rectal cancers that are MSI-high, immunotherapy can be considered in the neoadjuvant setting; AZUR-2 study is investigating dostarlimab vs standard of care (surgery or adjuvant chemotherapy) in T4N0 or stage III MSI-high colon cancer

Circulating tumor DNA (ctDNA)-guided management of colon cancer: DYNAMIC study (Tie et al [2022]) — patients with stage II CRC were randomized to standard management or ctDNA-guided adjuvant therapy; ctDNA-positive patients received chemotherapy, while ctDNA-negative patients were observed; the primary outcome was recurrence-free survival (RFS); at 2 yr, no difference in RFS was found between ctDNA-based and clinical-pathologic management, with fewer patients receiving chemotherapy in the ctDNA group, reducing toxicity; updated 5-yr results confirmed noninferiority, even in high-risk T4N0 tumors; in ctDNA-positive patients, persistent positivity after chemotherapy predicted worse outcomes

Management of liver metastases in colon cancer: TransMet study (Adam et al [2024]) — focused on patients with unresectable liver-only metastases; patients were randomized to receive a liver transplant plus chemotherapy or chemotherapy alone; criteria for liver transplant eligibility included unresectable liver metastases, no extrahepatic disease, stable response to chemotherapy, carcinoembryonic antigen response, and no BRAF mutations; most had bulky liver disease (50% with >20 nodules); 5-yr OS was significantly better for transplant plus chemotherapy (57%) vs chemotherapy alone (13%); recurrence occurred in 72%, mainly in the lungs, but 42% of transplant recipients remained disease-free at 50 mo; early referral and strict patient selection are critical

Readings

Adam R, Piedvache C, Chiche L, et al Collaborative TransMet group. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. Lancet. 2024 Sep 21;404(10458):1107-1118. doi: 10.1016/S0140-6736(24)01595-2; Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. Journal of Clinical Oncology. 2024;42(3_suppl):LBA768. doi:10.1200/jco.2024.42.3_suppl.lba768; Chalabi M, Verschoor YL, Tan PB, et al. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer. N Engl J Med. 2024 Jun 6;390(21):1949-1958. doi: 10.1056/NEJMoa2400634; Elez E, Kopetz S, Tabernero J, et al. SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC. Future Oncol. 2024 Apr;20(11):653-663. doi: 10.2217/fon-2022-1249; Lenz HJ, Van Cutsem E, Luisa Limon M, et al. First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II checkmate 142 Study. Journal of Clinical Oncology. 2022;40(2):161-170. doi:https://doi.org/10.1200/jco.21.01015; Tie J, Cohen JD, Lahouel K, et al; DYNAMIC Investigators. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Shergill is on the advisory board of Merus, Guardant, Pfizer, Regeneron/Sanofi, Catalyst Pharmaceuticals; is on the speaker's bureau of Takeda; has received grant/research support to his institution from Hutchinson MediPharma, Takeda, Merck, Verastem Oncology, Turning Point Therapeutics, Gritstone, Bolt Therapeutics, Bristol-Myers Squibb, Pfizer, Astellas, Oncologie, Macogenics, Seattle Genetics, Amgen, Daiichi, Lilly, Jacobio, AstraZeneca, Jazz Pharmaceuticals, and Agneus; and is a consultant at KLJ Associates. Members of the planning comittee reported nothing relevant to disclose. Dr. Shergill's lecture includes information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Shergill was recorded at University of Chicago Annual Practice Updates in Hematology and Oncology, held on August 9, 2024, in Oak Brook, IL, and presented by the University of Chicago Pritzker School of Medicine. For information on upcoming CME activities from this presenter, please visit cme.uchicago.edu. Audio Digest thanks the speakers and the University of Chicago Pritzker School of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

ON152302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.