Nivolumab May Help Some Patients With Refractory Biliary-Tract Cancer

By Will Boggs MD

May 13, 2020

NEW YORK (Reuters Health) - Nivolumab appears to provide objective responses in selected patients with advanced refractory biliary-tract cancer, a nonrandomized study suggests.

"There may be a role for immunotherapy in advanced biliary-tract cancer," Dr. Richard D. Kim of Moffitt Cancer Center, in Tampa, Florida, told Reuters Health by email. "I think the key to success is to either find a biomarker which can predict response to single-agent checkpoint inhibitors or a combination strategy where you combine checkpoint inhibitors with a different immunotherapy agent or tyrosine-kinase inhibitor."

Nivolumab, an antibody that blocks the ligation of programmed cell death 1 protein (PD-1) and programmed cell death 1 ligand 1 (PD-L1), has demonstrated durable clinical activity and safety in various cancers. A recent study identified PD-L1-expressing tumor cells in the tumor microenvironment of biliary-tract cancer, suggesting the possibility of PD-1 blockade immunotherapy.

Dr. Kim and colleagues evaluated the safety and efficacy of nivolumab in a single-arm, multicenter phase-2 study of 54 patients with advanced refractory biliary-tract cancer.

At the time of the current analysis, five patients were still receiving active treatment with nivolumab, 38 had discontinued treatment owing to disease progression, six had done so due to an adverse event and five had withdrawn consent.

Ten (22%) of 46 patients who had tumor-response evaluation with radiologic imaging achieved partial responses, and 17 (37%) achieved stable disease, for a disease-control rate of 59% per investigator assessment, the team reports in JAMA Oncology.

More than half of these patients (24/46, 52%) achieved disease control for 16 weeks or more, and four patients achieved partial responses lasting at least one year.

All patients who achieved partial responses had mismatch repair (MMR) protein-proficient tumors.

Median progression-free survival (PFS) was 3.68 months and median overall survival was 14.24 months.

Overall, nine patients (17%) developed grade-3 or -4 treatment-related adverse events, and 28 patients (52%) experienced immune-mediated adverse events.

Among 42 available tumor samples, 18 (43%) showed PD-L1 staining in tumor cells, including nine of 10 tumors from investigator-assessed responders and all five tumors from centrally assessed responders.

PD-L1 expression in tumor samples was associated with prolonged PFS, but not with overall survival. PD-L1-expressing tumor infiltrating lymphocytes (TILs), present in 52% of tumor samples, were not associated with clinical outcomes.

"More studies are warranted to possibly establish single-agent checkpoint inhibitor as an option in refractory biliary-tract cancer," Dr. Kim said. "Currently, there are many ongoing studies (of first-line treatment) and in refractory biliary-tract cancer with checkpoint inhibitors, mostly in combination with chemotherapy or targeted agents."

Dr. Mitesh J. Borad of Mayo Clinic, in Rochester, Minnesota, who recently reviewed targeted therapeutic strategies for biliary-tract cancers, told Reuters Health by email, "While this study reports promising findings, nivolumab remains an investigational therapy for biliary-tract cancers, and further studies will need to continue to explore its utility."

"Immunotherapy with agents such as checkpoint inhibitors is a promising area of study in biliary-tract cancer patients," said Dr. Borad, who was not involved in the research. "Hopefully, the results from this study will continue to stimulate ongoing efforts towards this end."

"Preliminary biomarker evaluation indicated that there may be an association between staining of PD-L1 by immunohistochemistry and outcomes such as PFS and overall survival, thereby laying out an approach to inform patient selection for future studies," he said.

Bristol-Myers Squibb funded the study. Dr. Kim and a colleague report financial ties to the company.

SOURCE: JAMA Oncology, online April 30, 2020.