A regular review of an FDA approval application is underway for the combination of pembrolizumab and standard chemotherapy for the treatment of advanced biliary tract cancer.
The FDA has set a Prescription Drug User Fee Act target action date of February 7, 2024, to decide on the approval application for pembrolizumab plus standard chemotherapy for advanced biliary tract cancer (BTC).1
The application is supported by results from the phase 3 KEYNOTE-966 study (NCT04003636).
Results from KEYNOTE-966 were most recently reported at the American Association for Cancer Research (AACR) 2023 Annual Meeting.
The FDA has accepted the supplemental biologics license application for the combination of pembrolizumab (Keytruda) and the standard-of-care (SoC) chemotherapy doublet, gemcitabine, and cisplatin, for the treatment of patients with locally advanced, unresectable, or metastatic BTC.
In the supporting clinical trial, KEYNOTE-966, a significant improvement in overall survival (OS) was achieved when pembrolizumab was added to SoC chemotherapy compared with SoC chemotherapy alone in patients with locally advanced, unresectable, or metastatic BTC who received treatment in the first-line.2
Specifically, at a median follow-up of 25.6 months (range, 18.3-38.4), gemcitabine and cisplatin plus pembrolizumab achieved a 17% reduction in the risk of death as first-line treatment for patients with locally advanced, unresectable, or metastatic BTC compared with gemcitabine and cisplatin alone (HR, 0.83; 95% CI, 0.72-0.95; P =.0034). The median OS observed was 12.7 months (95% CI, 11.5-13.6) with the addition of pembrolizumab vs 10.9 months (95% CI, 9.9-11.6) without.
At 1-year, the addition of pembrolizumab to gemcitabine and cisplatin showed an OS rate of 52% compared with 44% in the gemcitabine and cisplatin-only arm. At 2 years, the OS rates in the triblet arm vs the doublet arm were 24.9% vs 8.1%, respectively. The OS benefit observed with pembrolizumab added to gemcitabine and cisplatin in the overall population was consistent in the subgroup population evaluated.
For safety, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 70% of patients treated with pembrolizumab, gemcitabine, and cisplatin vs 69% of patients treated with gemcitabine and cisplatin alone. Death occurred in 2% of the pembrolizumab-treated patients compared with 1% of those who received SoC chemotherapy alone.
Safety results also showed that 7% of those treated with pembrolizumab plus SoC chemotherapy experienced grade 3 or 4 immune-mediated AEs vs 4% of those who received SoC chemotherapy alone. There were immune-mediated AEs leading to death in 1 patient treated with the combination of pembrolizumab, gemcitabine, and cisplatin.
1. FDA accepts application for Merck’s Keytruda® (pembrolizumab) plus chemotherapy as treatment for advanced or unresectable biliary tract cancer. News release. Merck. June 8, 2023. Accessed June 9, 2023. https://tinyurl.com/ycxwjn29
2. Merck’s Keytruda® (pembrolizumab) plus chemotherapy significantly improved overall survival compared to chemotherapy alone in patients with advanced or unresectable biliary tract cancer. News release. Merck, April 16, 2023. Accessed June 9, 2023. https://tinyurl.com/yarnm55x