Phase 2 study results suggest that the addition of nivolumab and ipilimumab to chemotherapy as first-line therapy did not provide additional PFS benefit compared to standard-of-care chemotherapy in patients with advanced biliary tract cancer.
The first-line treatment of patients with advanced biliary tract cancer was evaluated in a randomized, phase 2 multi-institutional study that compared the role of combination immunotherapy with nivolumab (Opdivo) plus ipilimumab (Yervoy) versus nivolumab plus chemotherapy with gemcitabine and cisplatin. Results of this study, which was led by Vaibhav Sahai, MBBS, MS, Leader, Gastrointestinal Medical Oncology Section, University of Michigan, Ann Arbor, were presented at this year’s annual meeting of the American Society of Clinical Oncology (ASCO).
Patients in arm A received gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 every 3 weeks plus nivolumab 360 mg on day 1 every 3 weeks for 6 months, followed by nivolumab 240 mg every 2 weeks as monotherapy for a total duration of 2 years. Patients in arm B received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks for 2 years or until disease progression.
The primary end point was progression-free survival (PFS) at 6 months. The secondary end points included best overall response rate (ORR) per immune-related Response Evaluation Criteria in Solid Tumors criteria, median PFS, overall survival (OS), and safety. Exploratory objectives included biomarker analysis using sequential whole exome/transcriptome and immune cell subsets in tissue and blood.
Enrolled in the study were a total of 64 eligible patients. Patients were divided in a 1:1 ratio to arm A or B, including 32 patients per arm. Patient median age was 62 years (range, 20-80 years); 90% of patients had metastatic disease.
At 6 months, PFS rate was 64.2% in arm A versus 23.4% in arm B. Median PFS rates were 7.4 months and 4.1 months in arm A and arm B, respectively. Median OS rates were 10.6 months and 8.3 months in arm A and arm B, respectively.
The PFS rate in arm B, which included the immunotherapy combination, was inferior to that in historical controls. However, the combination of immunotherapy plus chemotherapy in arm A was as effective as standard-of-care chemotherapy. A total of 40% of patients in arm A are still alive, suggesting that there may be a “tail” on the survival curve.
Still pending are analyses for safety and toxicity, ORR, genomic analysis, and immune subset analysis. The results in arm A of the study were not superior to those with standard-of-care chemotherapy. However, 2 phase 3 clinical trials are currently recruiting patients globally.
Source: Sahai V, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 4558.