Nivolumab Demonstrates Durable Response in Refractory Biliary Tract Cancer

May 12, 2020
Hannah Slater

The phase II study found that nivolumab was well tolerated and demonstrated moderate efficacy with durable response in patients with refractory biliary tract cancer.

A phase II study published in JAMA Oncology found that nivolumab (Opdivo) was well tolerated and demonstrated moderate efficacy with durable response in patients with refractory biliary tract cancer (BTC). 

However, the researchers indicated that further studies are necessary to verify the findings and assess biomarkers for improved treatment selection for patients. 

“With the success of PD-1 blockade immunotherapy in melanoma, nivolumab has been extensively suited in the treatment of multiple tumor types, and emerging clinical data have demonstrated durable clinical activity and safety of nivolumab in various cancers,” the authors wrote. “However, only limited are reported on the role of immune checkpoint inhibitors in BTC owing to the rarity of the disease.” 

In this single-group, multicenter phase II study of nivolumab, researchers assessed 54 patients with histologically confirmed BTC whose disease had progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy. Moreover, analysis was performed on an intention-to-treat basis. 

Participants were administered 240 mg of nivolumab intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. The primary endpoint was investigator-assessed objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AEs). 

Overall, 54 patients were enrolled in the trial and 46 were examined for objective response with radiologic imaging. The investigator-assessed ORR was 22%, including 1 unconfirmed partial response, which resulted in a disease control rate of 59%. Moreover, central independent review found an ORR of 11%, including 1 unconfirmed partial response, with a disease control rate of 50%. Notably, all of the patients who responded to treatment had mismatch repair protein-proficient tumors. 

Of the intention-to-treat population, median PFS was 3.68 months (95% CI, 2.30-5.69 months) and median OS was 14.24 months (95% CI, 5.98 months to not reached). Further, programmed cell death 1 ligand 1 expression in tumors was associated with prolonged PFS (HR, 0.23; 95% CI, 0.10-0.51; P < 0.001). 

“Our study suggests that PD-L1 expression in tumor cells should be assessed in future clinical trials with checkpoint inhibitors in BTC,” the authors wrote. 

The most common treatment-related adverse event (AE) was increased alkaline phosphatase (24%), followed by decreased lymphocytes (22%), increased aspartate aminotransferase (20%), and fatigue (20%). Grade 3 or 4 AEs were hyponatremia (6%) and increased alkaline phosphatase (4%). There were no treatment-related grade 5 AEs. 

“The durable response and safety profiles of nivolumab in our study are consistent with other PD-1 and PD-L1 blockade agents, including durvalumab and pembrolizuamb, for patients with BTCs,” the authors wrote.

Researchers indicated that the findings presented in the current study need to be validated in larger clinical trials, as they were limited to a relatively small sample cohort and lacked a control group. 


Kim RD, Chung V, Alese OB, et al. A Phase 2 Multi-Institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. JAMA Oncology. doi:10.1001/jamaoncol.2020.0930.