Fresh off ESMO 2026, Drs. Nicholas Hornstein and Timothy Brown return to The Gut-Onc Lab to break down the most impactful gastrointestinal oncology data and revisit their pre-conference predictions. From emerging Claudin 18.2 antibody-drug conjugates (ADCs) and PD-1/VEGF bispecifics to landmark immunotherapy results and chemotherapy optimization, the panel examines which findings are ready to change clinical practice, which require further validation, and what comes next for GI cancer care.
Key Discussion Points
–Upper GI: ADCs, HER2-Targeted Therapy & Organ Preservation:
- G-HOPE-001 (LBA77): Reviewing Phase III results for arcotatug tavatecan in previously treated CLDN18.2-positive gastric cancer, highlighting improved median overall survival (OS; 10.2 vs. 6.9 months) and objective response rates (37.4% vs. 7.7%), while discussing biomarker thresholds and applicability to Western populations.
- CLARITY-Gastric01 (LBA7): Examining sonesitatug vedotin’s significant OS benefit despite missing its progression-free survival (PFS) endpoint, alongside broader CLDN18.2 eligibility, gastrointestinal toxicity, and potential movement into earlier treatment lines.
- Long-Term SANO: Assessing extended follow-up supporting watch-and-wait strategies and organ preservation for selected patients with esophageal cancer who achieve a clinical complete response.
- HERIZON-GEA-01: Discussing updated survival outcomes with zanidatamab, tislelizumab, and chemotherapy in HER2-positive gastroesophageal adenocarcinoma, including median OS reaching 26.4 months and the potential role of HER2 expression in treatment selection.
–Biliary Tract Cancer: Emerging Therapies & Adjuvant Treatment Standards:
- ACTICCA-1: Evaluating why adjuvant gemcitabine plus cisplatin failed to significantly improve disease-free survival over capecitabine following biliary tract cancer resection, reinforcing capecitabine’s continued role as the standard of care.
- HARMONi-GI1 (LBA8): Analyzing Phase III results for ivonescimab, a PD-1/VEGF bispecific, plus chemotherapy versus durvalumab plus chemotherapy in advanced biliary tract cancer. The panel discusses the significant OS benefit (HR 0.75), safety considerations, and the need for validation in Western populations.
–MSI-High Colorectal Cancer: Immunotherapy & Organ Preservation:
- CheckMate-8HW Final OS (LBA32): Examining final survival results supporting nivolumab plus ipilimumab in dMMR/MSI-high metastatic colorectal cancer, including the advantages of dual checkpoint inhibition over monotherapy and practical management of immune-related toxicities.
- AZUR-1 (LBA37): Reviewing dostarlimab monotherapy in 154 patients with locally advanced dMMR/MSI-high rectal cancer, including the 68% investigator-assessed sustained clinical complete response rate, organ preservation strategies, and the implications of recent FDA accelerated approval.
–Colorectal Cancer: BRAF-Targeted Therapy & Chemotherapy Optimization:
- ECLIPSE Phase II: Exploring the continuation of encorafenib plus cetuximab beyond progression with FOLFIRI in BRAF V600E-mutated metastatic colorectal cancer, highlighting encouraging PFS findings and the rationale for sustained MAPK pathway inhibition.
- IROCAS Phase III: Discussing the failure of intensified adjuvant mFOLFIRINOX to improve disease-free survival over mFOLFOX6 in high-risk stage III colon cancer, reinforcing the limitations of chemotherapy escalation.
- PRABITAS Phase III: Highlighting an alternative trifluridine/tipiracil plus bevacizumab dosing schedule that preserved efficacy while reducing severe neutropenia from 39% to 13%, offering a simpler and potentially better-tolerated approach for refractory metastatic colorectal cancer.
Chapters:
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