“Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1–expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC,” the study authors wrote.
This was a single-group, multicenter phase 2 study of patients with histologically confirmed BTC. Eligible patients experienced disease progression while being treated with between one and three lines of systemic therapy. Enrollment was performed between Oct. 5, 2016, and Dec. 26, 2018. An intention-to-treat basis was used to perform analysis. For 16 weeks, patients received nivolumab 240 mg intravenously every two weeks; they then received 480 mg intravenously every four weeks until either disease progression or unacceptable toxic effects. The main outcome was investigator-assessed objective response rate; additional outcomes included progression-free survival, overall survival, and incidence of adverse events.
The study enrolled 54 patients (median age, 65 years; women, n=27; men, n=27), of whom 46 (median age, 65 years; women, n=24; men, n=22) underwent radiologic imaging to assess objective response. The investigator-assessed objective response rate was 22% (including one unconfirmed partial response), with a disease control rate of 59%, and the central independent review yielded an 11% objective response rate (including one unconfirmed partial response), with a disease control rate of 50%. Patients who responded to treatment were classified as responders. Mismatch repair protein-proficient tumors were observed in all responders. In the intent-to-treat patients, median progression-free and overall survival was 3.68 months and 14.24 months, respectively. A correlation was observed between programmed cell death 1 ligand 1 expression in tumors and prolonged progression-free survival. The most prevalent treatment-related grade 3 or 4 toxic events were hyponatremia, presenting in three patients, and increased alkaline phosphatase, presenting in two patients.
The results were published in JAMA Oncology.
“This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients,” the researchers wrote in summary.