A randomized multicenter study of a combination of immunotherapy with a targeted therapy improved cancer control for some patients with biliary tract cancer, according to research presented by Yarchoan et al at the American Association for Cancer Research (AACR) Virtual Annual Meeting (Abstract CT043).  

Biliary tract cancer represents about 3% of all gastrointestinal cancers. The standard therapy for patients who have advanced disease is a combination of the chemotherapy agents gemcitabine and cisplatin, but the survival of patients receiving standard treatment is less than 1 year. Presenting author Mark Yarchoan, MD, Assistant Professor of Oncology at the Johns Hopkins Kimmel Cancer, explained that some patients with biliary tract cancer may have particular mutations for which a precision medicine approach with drugs that specifically target these mutations can be beneficial. For example, a small number of patients with biliary tract cancer have mismatch repair–deficient tumors (MMR-d), and researchers at the Johns Hopkins Kimmel Cancer previously discovered that MMR-d tumors can be effectively treated with pembrolizumab. However, the majority of patients with biliary tract cancer do not have any “actionable” mutations in their tumor, and for these patients the standard of care has not changed significantly since 2010, said Dr. Yarchoan.

“We wanted to see if combining the two drugs resulted in improved anticancer activity in biliary tract cancer,” said Dr. Yarchoan. To find out if the combination was effective, he and his collaborators opted to compare the benefit of atezolizumab alone vs atezolizumab plus cobimetinib in a randomized study.

Methods

The study included 86 patients with advanced biliary tract cancer. Participants were aged 44 to 86 years; 62% (48) were female; and could have received one or two prior treatments for biliary tract cancer. Patients were randomly assigned to receive atezolizumab alone or atezolizumab in combination with cobimetinib.

Findings

Among the patients who enrolled in the study, 77 completed at least one dose of therapy (39 in the single-treatment arm and 38 patients in the combination treatment arm). Progression-free survival in the combination therapy group was nearly double (111 days) than that seen in the single treatment arm (57 days). This difference in progression-free survival met the study primary endpoint and was statistically significant. There was one partial response (3.2%) and 13 patients with stable disease (41.9%) in the combination arm, and one partial response (2.9%) and 10 patients with stable disease (29.4%) in the atezolizumab monotherapy arm.

The disease control rate was 14 of 31 patients whose treatment could be measured (45.2%) in the combination treatment arm, and 11 of 34 patients (32.4%) in the single-treatment arm. Two patients, both receiving combination treatment, remained in the study more than 15 months from study enrollment.

Side effects of the combination were manageable and included nausea, vomiting, rash, and low blood and platelet counts. There were no treatment-related deaths, but 12 patients (4 receiving atezolizumab alone and 8 receiving the combination) stopped treatment due to various side effects.

“The low response rates in both treatment groups highlights the challenge of immunotherapy in biliary tract cancer,” said Dr. Yarchoan. “However, the combination of atezolizumab with cobimetinib met its primary outcome and significantly prolonged progression free survival as compared to atezolizumab. This combination warrants further clinical investigation.”

Disclosure: The study was supported by the National Cancer Institute and F. Hoffmann-LaRoche, Ltd. For full disclosures of the study authors, visit abstractsonline.com.