Early-Stage Study of Nivolumab Alone or in Combination With Cisplatin/Gemcitabine in Biliary Tract Cancer
In a Japanese phase I trial reported by Ueno et al in The Lancet Gastroenterology & Hepatology, researchers found nivolumab showed activity and had a manageable safety profile in patients with unresectable or recurrent biliary tract cancer.
Methods
The open-label phase I trial was conducted at four sites and enrolled 60 patients aged 20 to 79 years in 2016 and 2017. Patients with disease that was refractory or intolerant to gemcitabine-based treatment were assigned to receive nivolumab monotherapy (240 mg every 2 weeks) (n = 30). Patients who were chemotherapy-naive were assigned to receive nivolumab 240 mg/every 2 weeks and cisplatin 25 mg/m2 plus gemcitabine 1,000 mg/m2 (n = 30).
Eligible patients had biliary tract adenocarcinoma (intrahepatic bile duct cancer, extrahepatic bile duct cancer, gallbladder cancer, or ampullary cancer); Eastern Cooperative Oncology Group performance status 0 or 1; adequate hepatic, renal, and hematological function; and tumor tissue samples for programmed cell death ligand 1 (PD-L1) expression analysis.
The primary endpoint was tolerability and safety of the treatment.
Response
In patients treated with nivolumab monotherapy, median overall survival was 5.2 months vs 15.4 months in patients treated with combination therapy. Median progression-free survival was 1.4 months in the nivolumab group vs 4.2 months in the combination group. One of 30 patients treated with nivolumab monotherapy had an objective response vs 11 of 30 patients treated with the combination therapy.
Safety
In the monotherapy group, the most common treatment-related adverse events were decreased appetite (17% of patients), malaise (13%), and pruritus (13%). Grade 3–4 events occurred in three patients (rash, maculopapular rash, and amylase increase, respectively) and a serious treatment-related adverse event occurred in one patient (pleurisy).
In the combination therapy group, the most common treatment-related adverse events were neutrophil count decrease (any grade = 83%, grade 3–4 = 77%), and platelet count decrease (any grade = 83%, grade 3–4 = 50%). There were 11 serious treatment-related adverse events reported by six patients—platelet count decrease, febrile neutropenia, neutrophil count decrease, anemia, anaphylactic reaction, decreased appetite, pyrexia, and myocarditis.
The researchers concluded, “Nivolumab had a manageable safety profile and signs of clinical activity in patients with unresectable or recurrent biliary tract cancer. This initial assessment of nivolumab for the treatment of advanced biliary tract cancer provides supportive evidence for future larger randomized studies of nivolumab in this difficult-to-treat cancer.”
Disclosure: The study was funded by Ono Pharmaceutical and Bristol-Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
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