Multicenter phase 2 study of nivolumab plus ipilimumab with radiotherapy for metastatic, microsatellite stable colorectal cancer

Immune checkpoint inhibitors (ICIs) have significantly altered the natural history of microsatellite intability high metastatic colorectal cancer (mCRC). A multicenter phase 2 study in Boston (MA) evaluated combined radiotherapy (RT) with ICI therapy in microsatellite stable (MSS) refractory mCRC. The study enrolled 30 patients with MCC mCRC previouly treated with oxaliplatin, 5-fluorouracil, and irinotecan. Patients received RT plus nivolumab and ipilimumab. The primary endpoint was the objective response rate (ORR) for unirradiated lesions. For these lesions, the confirmed ORR was 10%, and the disease control rate (DCR) was 33%. For irradiated lesions, the ORR was 13.3% and the DCR was 83.3). Among 8 patients without active liver metastases, ORR was 25.0% (95% CI 3.2-65.1) whereas among 22 patients with liver metastases, ORR was 4.6% (0.1-22.8). Median progression-free survival was 2.4 months, and median overall survival was 12.8 months. Treatment was tolerable, with grade 4 toxicity in 10% of patients (lymphopenia in all cases). The authors conclude that the combination of immune-modulating, non-ablative doses of RT with nivolumab plus ipilimumab has selective clinical activity in refractory MSS mCRC, with responses concentrated primarily in patients without active liver metastases.