Combined CTLA-4/PD-1 blockade using ipilimumab and nivolumab has demonstrated superior efficacy compared with single-agent anti–PD-1 therapy in patients with advanced melanoma and renal-cell carcinoma.1 The authors aimed to test this combination in patients with metastatic biliary tract cancer (BTC).2
A total of 39 patients with metastatic BTC were enrolled. Patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks. Treatment continued for up to 96 weeks, or until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1 criteria. The primary end point was disease control rate (complete response + partial response + stable disease). Exploratory end points included correlation of efficacy with biomarkers, including PD-L1 expression and tumor mutation burden. A total of 33 (85%) patients had received at least 1 prior line of systemic treatment (0-2 lines).
The overall response rate was 24%, the disease control rate was 44%, and the median duration of response was not reached (range, 2-26+ months). Responses were observed in 5 of 16 intrahepatic, 0 of 10 extrahepatic, and 4 of 13 gallbladder cancer patients. None of the responding patients demonstrated tumors with microsatellite instability. Two patients with durable partial responses were subsequently rendered surgically free of disease. Median overall survival and progression-free survival were 5.7 and 2.9 months, respectively. Twenty-two (56%) patients experienced an immune-related adverse event, with grade 3/4 immune-related adverse events being observed in 5 (17%) patients.
The authors concluded that the combination of ipilimumab and nivolumab demonstrated significant clinical activity in patients with microsatellite stable tumors. ClinicalTrials.gov number NCT02923934.
