Nivolumab with Chemotherapy or with Ipilimumab as First-Line Therapy for Patients with Advanced Unresectable Biliary Tract Cancer

Arandomized, phase 2 multi-institutional study compared the role of combination immunotherapy with nivolumab (Opdivo) plus ipilimumab (Yervoy) versus nivolumab plus chemotherapy with gemcitabine and cisplatin in the first-line treatment of patients with advanced biliary tract cancer.

The study was led by Vaibhav Sahai, MBBS, MS, Leader, Gastrointestinal Medical Oncology Section, University of Michigan, Ann Arbor, and the results were presented at the 2020 ASCO annual meeting.

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 study’s 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. The exploratory objectives included biomarker analysis using sequential whole exome/transcriptome and immune cell subsets in tissue and blood.

A total of 64 eligible patients were enrolled in the study and were divided in a 1:1 ratio to arm A or arm B, including 32 patients in each arm. The patients’ median age was 62 years (range, 20-80 years), and 90% of them had metastatic disease.

At 6 months, the PFS rate was 64.2% in arm A versus 23.4% in arm B. The median PFS was 7.4 months in arm A and 4.1 months in arm B. The median OS was 10.6 months in arm A and 8.3 months in arm B.

The PFS in arm B, which included the immunotherapy combination, was inferior to historical controls, but 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, which suggests that there may be a “tail” on the survival curve.

Analyses are still pending for safety and toxicity, ORR, genomic analysis, and immune subset analysis.

Although the results in arm A of the study were not superior to results with standard-of-care chemotherapy, 2 phase 3 clinical trials are currently recruiting patients globally.