Abstract Background: In the randomized phase 3 KEYNOTE-966 trial, first-line pembrolizumab plus chemotherapy significantly improved overall survival (OS) versus placebo plus chemotherapy for participants with advanced biliary tract cancer. This post hoc analysis investigated whether hepatitis B virus (HBV) infection affected the efficacy and safety of pembrolizumab plus chemotherapy. Methods: Eligible participants had histologically confirmed extrahepatic or intrahepatic cholangiocarcinoma or gallbladder cancer, unresectable locally advanced or metastatic disease measurable per RECIST v1.1, known HBV and hepatitis C virus (HCV) status (including active HBV), and ECOG performance status 0 or 1. Participants were randomly assigned 1:1 to intravenous pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for ≤35 cycles plus gemcitabine and cisplatin. HBV-positive participants were monitored for HBV reactivation, and antiviral therapy was required for chronic HBV infection. The primary end point was OS. Results: The intention-to-treat population comprised 1069 participants (533, pembrolizumab group; 536, placebo group). The median time from randomization to data cutoff (November 14, 2023) was 36.6 months (range, 29.2-49.4). Among 329 HBV-positive participants (30.8%), 30 had chronic and 299 had clinically resolved HBV. OS HR was 0.87 (95% CI, 0.69-1.10) with pembrolizumab versus placebo for the HBV-positive subgroup and 0.85 (95% CI, 0.73-0.99) for the HBV-negative subgroup. Safety was consistent between the subgroups. Eight participants had HBV reactivation (5, pembrolizumab group; 3, placebo group) and no cases of HBV-associated hepatitis occurred in either group. Conclusions:Efficacy and safety outcomes were consistent between HBV-positive and HBV-negative participants receiving first-line pembrolizumab compared with placebo plus gemcitabine and cisplatin.
Chan et al. (Thu,) studied this question.
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