Regorafenib Plus Nivolumab Fails to Improve Outcomes in Gastric or Gastroesophageal Cancer
Key Clinical Takeaways
- Design/Population:This multinational, investigator-initiated randomized study evaluated regorafenib plus nivolumab versus standard chemotherapy in patients with third-line or later advanced gastrointestinal cancers. More than 400 patients were enrolled across 89 international centers, reflecting a real-world, heavily pretreated population with limited therapeutic options.
- Key Outcomes: The combination of regorafenib and nivolumab did not improve outcomes compared with chemotherapy, with no superiority observed in overall survival or progression-free survival. However, a small subset of patients experienced durable responses, suggesting potential biologic sensitivity to immunotherapy–TKI combinations that warrants further exploration.
- Clinical Relevance: Although the regimen did not outperform chemotherapy, the study underscores the importance of identifying biomarkers of benefit and refining non-cytotoxic combination strategies for refractory GI cancers. Robust translational analyses from this large trial are expected to help guide future precision immunotherapy approaches and optimize patient selection.
David Goldstein, MD, Prince of Wales Hospital, Sydney, Australia, discusses results from the INTEGRATE study, which evaluated regorafenib plus nivolumab versus standard chemotherapy in previously treated patients with gastric or gastroesophageal cancer.
Results showed that the combination was inferior to investigator’s choice chemotherapy, underscoring the need to develop more effective non-chemotherapy regimens incorporating regorafenib.
These findings were presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
Source:
Goldstein D, Sjoquist K, Espinosa D, et al. Regorafenib plus nivolumab vs investigator’s choice of chemotherapy in previously treated gastric or gastroesophageal cancer: INTEGRATE IIb, a randomized phase 3 AGITG Intergroup [NHMRC-CTC/IKF/AIO, ACCRU, TCOG/NHRI] study. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA80
