What are your top takeaways from ASCO GI 2025?

1. BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer. This ambitious phase 3 randomized trial is an initiative of project frontrunner to attempt to allow access of targeted therapy in earlier lines of treatment for advanced cancer patients.

Patients were randomized 1:1 to receive encorafenib + FOLFOX, or SOC (FOLFOX, CAPOX, or FOLFOXIRI). Dual primary endpoints were ORR (assessed in the first 110 patients randomized to eac...

1. The addition of pamrevlumab to gemcitabine and abraxane did not improve mOS in patients with metastatic pancreatic cancer. This is disappointing news again for a combination with sound rationale behind it. Fifty percent of the patients had matched pre-and on-treatment tumor biopsies, and I remain hopeful the analysis of these samples will provide critical insights for the next steps.
   
   
2. The BREAKWATER trial was overwhelmingly positive and confirms encorafenib + cetuximab + chemotherapy as a new fi...

1. BREAKWATER study confirming encorafenib/cetuximab/FOLFOX as the preferred first-line agent for metastatic BRAF V600E mutated colorectal cancer - this is practice changing. Kopetz et al., JCO 2025
2. CheckMate 8HW - Ipilumimab/nivolumab is the superior first-line regimen for MSI-high/deficient MMR metastatic colorectal cancer Andre et al., JCO 2025 - I think many of us were doing this already but this is great confirmation supporting that approach.
3. EORTC-1203 GITC "INNOVATION" trial looked at ...

ASCO GI 2025 provided a forum to present some thought-provoking studies which should augment standard of care for patients, particularly with colorectal cancer.

1. First I would highlight a presentation from the NCI cooperative groups CALGB (Alliance)/SWOG which discussed study 80702 for stage III colon cancer. The trial included adjuvant treatment with 3 versus 6 months of FOLFOX with or without adjuvant celecoxib and also explored the prognostic and predictive role of circulating tumor DNA obtai...

1. CheckMate 8HW – new first-line SOC of ipi/nivo for dMMR/MSI-H advanced CRC
2. BREAKWATER – new first line SOC of FOLFOX + encorafenib + cetuximab for BRAFV600E mutated advanced CRC
3. RMC-6236-001 – RAS(ON) inhibitor showing some impressive activity in patients with RAS mutations, particularly G12X
4. ALASCCA – adjuvant low dose ASA (160 mg) for stage I-III colorectal with PI3K mutations. Reduced risk of recurrence by 50%.
5. RESET-C – One neoadjuvant cycle of pembro for stage I-III dMMR colorectal cancer....

1. 80702 ctDNA Prediction in Celecoxib People

• ctDNA predicts relapse as DFS is 33% vs 85% in ctDNA negative
• Celecoxib didn't help ctDNA negative patients but did help ctDNA positive.

Celecoxib may be beneficial in reducing colorectal recurrence in patients with ctDNA positivity after surgery. (80702).

2. FOLFOX + Encorafenib + Cetuximab is the new first-line therapy for BRAF V600E mutated colorectal cancers, moving this treatment-targeted treatment up in the front line from the second line (BR...

1. CheckMate 8HW study: this study design was not very clearly stated but we need to be aware that there are two major parts within this study: Nivolumab/Ipilimumab vs chemotherapy in the first line setting. That part was reported last year in NEJM that showed immunotherapy provided better PFS in dMMR metastatic colorectal cancer patients which is not surprising at all since we already know that single agent immunotherapy is better than chemotherapy based on the phase III KEYNOTE-177 and phase II ...

1. The BREAKWATER trial: Practice changing data for patients with BRAF V600 mutated MSS CRC, particularly based on OS benefit noted in the study. Although most of the data is not mature, the FDA granted accelerated approval given there is a huge unmet need for patients with this aggressive biology. Nonetheless, we will be looking forward to seeing more mature data from this study.
   
   
2. CheckMate 8WH: This study once again shows Nivolumab + Ipilimumab is one of the standard-of-care therapies and the add...