Pembrolizumab plus Gemcitabine and Cisplatin for Advanced Biliary Tract Cancer

A prior randomized, phase 3 study showed that adding the anti–PD-L1 immune checkpoint inhibitor durvalumab to first-line chemotherapy with gemcitabine and cisplatin significantly improved overall survival in patients with advanced biliary cancer (NEJM JW Oncol Hematol Aug 2022 and NEJM Evid 2022 Jun 1; [e-pub]).

Now, to evaluate the anti–PD-1 immune checkpoint inhibitor pembrolizumab in this setting, investigators conducted an industry-sponsored, international, randomized, phase 3 trial (KEYNOTE-966) in which 1609 untreated patients with advanced biliary cancer received treatment every 3 weeks with gemcitabine (no maximum duration), cisplatin (maximum, 8 cycles), and pembrolizumab or placebo (maximum, 35 cycles). Among the patients, 45% were treated in Asia, 59% had intrahepatic primaries, 88% had metastatic disease, and 68% had a PD-L1 combined positive score of ≥1%.

At a median follow-up of 25.6 months, overall survival (OS; the primary endpoint) was longer with pembrolizumab than with placebo (12.7 vs. 10.9 months; hazard ratio, 0.83; P=0.0034); OS rates were improved with pembrolizumab at 12 months (52% vs. 44%) and 24 months (25% vs. 18%). The level of PD-L1 expression had no impact on OS benefit. Progression-free survival was similar with or without pembrolizumab (6.5 and 5.6 months, respectively). The rate of response was similar in both arms (29%); the median duration of response was 9.7 months with pembrolizumab and 6.9 months with placebo. No new safety signals were identified.