Preliminary data suggest that dual blockade with ipilimumab and nivolumab might have antitumor activity in a subset of patients with microsatellite-stable biliary tract cancer.
In a previous study of patients with advanced melanoma and renal-cell carcinoma,1 the combination of a CTLA-4 inhibitor and a PD-1 inhibitor with ipilimumab (Yervoy) and nivolumab (Opdivo) has shown superior efficacy compared with single-agent anti–PD-1 therapy. A study presented at this year’s virtual meeting of the American Society of Clinical Oncology (ASCO) included patient populations with rare tumors, including a subset of patients with biliary tract cancer. In the cohort of patients with metastatic biliary tract cancer,2 the benefit of this dual blockade with ipilimumab and nivolumab was analyzed by study investigators, led by Oliver Klein, MD, FRACP, Olivia Newton-John Cancer Research Institute, Heidelberg, Australia.
A total of 39 patients with metastatic biliary tract cancer were included in the study. The 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 ≤96 weeks or until disease progression or unacceptable toxicity. Response to therapy was assessed every 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1.
The primary end point was disease control rate—complete response plus partial response plus stable disease. Exploratory end points included the correlation of efficacy with biomarkers, including PD-L1 expression and tumor mutation burden. A total of 33 (85%) patients had previously received at least 1 (range, 0-2) line of systemic treatment.
The overall response rate was 24%, disease control rate was 44%, and median duration of response was not reached (range, 2-≥26 months). Responses were observed in 5 of the 16 patients with intrahepatic CCA, in none of the 10 patients with extrahepatic CCA, and in 4 of the 13 patients with gallbladder cancer. None of the responding patients had tumors with microsatellite instability. In addition, 2 patients with durable partial responses were subsequently rendered surgically free of disease.
Median overall survival was 5.7 months, and progression-free survival was 2.9 months. A total of 22 (56%) patients had an immune-related adverse event, including 6 (17%) patients with grade 3 or 4 events.
The investigators concluded that in patients with microsatellite-stable biliary tract cancer, the combination of ipilimumab and nivolumab showed significant clinical activity.
References
- Chae YK, Arya A, Iams W, et al. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6:39.
- Klein O, Kee D, Nagrial A, et al. Combination immunotherapy with ipilimumab and nivolumab in patients with advanced biliary tract cancers. J Clin Oncol. 2020;38(15_suppl):Abstract 4588.