Overview
This episode of the Oncology Brothers podcast, featuring Dr. Kathy Eng from Vanderbilt, reviews five key abstracts on gastrointestinal (GI) cancers presented at the ASCO 2025 conference, with a focus on practice-changing studies in colorectal and upper GI malignancies.
Dynamic-III: CTDNA-Guided Therapy in Stage III Colon Cancer
- The Dynamic-III study examined escalation of adjuvant chemotherapy based on positive circulating tumor DNA (CTDNA) after surgery in stage III colon cancer.
- Escalating treatment for CTDNA-positive patients did not improve recurrence-free survival.
- CTDNA remains a strong prognostic marker but is not predictive for benefit from intensified chemotherapy in this setting.
- In clinical practice, CTDNA testing is selectively used, mainly to adjust surveillance intervals rather than treatment plans.
Atomic Trial: Immunotherapy in MSI-High Stage III Colon Cancer
- Atomic trial assessed adding atezolizumab to FOLFOX chemotherapy in stage III microsatellite instability-high (MSI-high) colon cancer.
- The combination improved disease-free survival, achieving a hazard ratio of 0.5.
- The trial supports immunotherapy as adjuvant treatment in MSI-high stage III colon cancer, potentially redefining standard care.
- Duration and regimen specifics may evolve as guidelines adapt.
Breakwater Study: BRAF V600E Mutant Metastatic Colorectal Cancer
- Breakwater trial evaluated encorafenib and cetuximab with FOLFOX as first-line therapy for BRAF V600E mutant colorectal cancer.
- The regimen doubled median overall survival to 30.3 months, compared to 15 months for standard therapy.
- Common side effects include rash, diarrhea, fatigue, and myelosuppression; careful management is required.
Matterhorn Study: Dervalumab in Resectable Gastric and GE Junction Cancer
- Matterhorn study tested perioperative dervalumab with FLOT chemotherapy in locally advanced, resectable gastric and gastroesophageal junction adenocarcinoma.
- Event-free survival significantly improved in the investigational arm.
- The approach is likely to set a new standard of care once available.
DESTINY-Gastric04: TDXD in HER2-Positive Gastric Cancer
- Destiny-Gastric04 compared trastuzumab deruxtecan (TDXD) with standard care in HER2-positive metastatic gastric or GEJ cancer after at least one prior therapy.
- TDXD improved overall survival and progression-free survival, establishing it as the preferred second-line option.
- High-dose regimens are standard in gastric cancer; side effects include fatigue, nausea, alopecia, and potential mortality.
Key Takeaways from ASCO 2025 GI Malignancy Studies
- CTDNA positivity is prognostic, not predictive for chemotherapy benefit in stage III colon cancer.
- Adjuvant immunotherapy improves outcomes in MSI-high stage III colon cancer.
- Encorafenib/cetuximab plus chemotherapy is a new standard for BRAF V600E mutant metastatic colorectal cancer.
- Dervalumab plus FLOT perioperatively improves outcomes in resectable gastric/GEJ cancer.
- TDXD is confirmed as the preferred second-line therapy for HER2-positive metastatic gastric cancer.