Immunotherapy response in microsatellite stable metastatic colorectal cancer is influenced by site of metastases

Background: Prior studies indicate that colorectal cancer patients with liver metastases did not benefit from regorafenib, nivolumab (REGONIVO) or regorafenib, ipilimumab, nivolumab (RIN) treatments, while those without liver metastases showed significant response. This study explores the impact of metastatic sites on treatment outcomes.Methods: Chemotherapy-refractory colorectal cancer patients treated with REGONIVO or RIN were evaluated, focusing on 2-month organ-specific response, ORR, PFS and OS based on metastatic sites.Results: Of the 96 patients analyzed (58 REGONIVO, 38 RIN), liver or peritoneal metastases led to poor outcomes, with 0 % ORR, and median PFS of 2.0 and 1.5 months respectively. In contrast, lung-only metastases had an ORR of 56.3 % and a PFS of 14 months. The presence of concurrent LN or other extrahepatic metastatic disease in patients with lung metastatic disease diminished but did not prohibit responses. The 2-month response assessment revealed activity in the lungs, soft tissues, and distant lymph nodes.Conclusions: REGONIVO and RIN were most active in lung-only metastases. Liver and peritoneal metastases were resistant. Future checkpoint inhibitor trials in MSS colorectal cancer should stratify patients based on metastatic locations.