The 2025 Gastrointestinal Cancers Symposium highlighted significant advancements in the treatment of various gastrointestinal malignancies. Presentations covered novel immuno-oncology agents, chemotherapeutic strategies, and targeted therapies, offering new hope for patients with these challenging cancers. Key studies focused on colorectal, hepatocellular, and esophageal cancers, showcasing improved outcomes and potential shifts in treatment paradigms.
CheckMate 8HW: Nivolumab/Ipilimumab in MSI-H/dMMR mCRC
The phase 3 CheckMate 8HW trial (NCT04008030) revealed that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) significantly improved progression-free survival (PFS) compared to nivolumab monotherapy in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). The median PFS was not reached for the combination arm (95% CI, 53.8 months-NE) versus 39.3 months for nivolumab alone (95% CI, 22.1-NE; HR, 0.62; 95% CI, 0.48-0.81; P = .0003).
Thierry André, MD, stated that these results, combined with previous findings, establish nivolumab plus ipilimumab as a new standard of care for patients with MSI-H/dMMR metastatic CRC.
BREAKWATER: Encorafenib/Cetuximab Plus Chemotherapy in BRAF V600E+ mCRC
The phase 3 BREAKWATER trial (NCT04607421) demonstrated that adding encorafenib (Braftovi) and cetuximab (Erbitux) to standard-of-care mFOLFOX6 chemotherapy significantly improved the overall response rate (ORR) in patients with BRAF V600E-mutated mCRC. The ORR was 60.9% (95% CI, 51.6%-69.5%) with the combination versus 40.0% (95% CI, 31.3%-49.3%) for mFOLFOX6 alone (odds ratio, 2.443; 95% CI, 1.403-4.253; one-sided P = .0008).
These data supported the FDA's accelerated approval of encorafenib in combination with cetuximab and mFOLFOX6 for this patient population in December 2024. Tanios S. Bekaii-Saab, MD, noted that these results could transform practice by establishing this combination as the standard of care.
CARES-005: Camrelizumab/Rivoceranib Plus TACE in Unresectable HCC
The phase 2 CARES-005 trial (NCT04559607) showed that combining camrelizumab, rivoceranib, and transarterial chemoembolization (TACE) led to a statistically significant improvement in PFS compared to TACE alone in patients with unresectable hepatocellular carcinoma (HCC). The median PFS was 10.8 months (95% CI, 8.8-13.7) for the combination versus 3.2 months (95% CI, 2.4-4.2) for TACE alone (HR, 0.34; 95% CI, 0.24-0.50; P < .0001).
Gao-Jun Teng, MD, highlighted that the safety profile of the combination was manageable and consistent with the known adverse effect profiles of the individual agents.
Other Notable Studies
- DRAGON-01: Intraperitoneal and intravenous paclitaxel plus S-1 (NIPS) improved overall survival (OS) compared to intravenous paclitaxel and S-1 alone (PS) in patients with gastric cancer and peritoneal metastasis (HR, 0.66; 95% CI, 0.49-0.88; P = .0056).
- SCIENCE: Adding sintilimab to neoadjuvant chemoradiotherapy (CRT) improved pathological complete response (pCR) rates in resectable locally advanced esophageal squamous cell carcinoma (ESCC).
- CheckMate 9DW: Nivolumab plus ipilimumab demonstrated a median OS of 23.7 months vs 20.6 months for lenvatinib or sorafenib (HR, 0.79; 95% CI, 0.65-0.96; P = .018) in patients with previously untreated unresectable hepatocellular carcinoma (HCC).
The 2025 Gastrointestinal Cancers Symposium provided valuable insights into emerging treatment strategies, with several studies poised to influence clinical practice and improve outcomes for patients with gastrointestinal malignancies.
