Comparative efficacy and safety of durvalumab and pembrolizumab combined with chemotherapy in advanced cholangiocarcinoma: A meta-analysis.

Abstract

576 Background: Cholangiocarcinoma (CAA) is a rare gastrointestinal malignancy by aggressive behavior and poor prognosis. It is classified based on its anatomical location into intrahepatic, perihilar, and distal subtypes. Chemotherapy has remained the stander first-line treatment for over a decade, with a median overall survival (OS) of 11 months in patients with locally advanced or metastatic CCA. Immunotherapy (IO) has emerged as an effective strategy across multiple cancer types and has demonstrated promising efficacy when combined with chemotherapy in CCA. However, data on IO therapy compared head-to-head are limited. In this meta-analysis aims to assess the benefit of IO-based regimens for efficacy and safety using phase 3 clinical trial (RCTs). Methods: We performed a systematic search of studies published from 8 November 2023, focusing on phase 3 RCTs that assessed durvalumab or pembrolizumab in combination with gemcitabine plus cisplatin (GemCis) and reported outcomes for OS, PFS, and adverse events (AEs) based on Common Terminology Criteria of Adverse Events (CTCAE). For studies presenting Kaplan-Meier curves, individual patient data (IPD) tool was used to reconstruct the data for outcome calculations. Results: A total of 874 patients with unresectable or metastatic CCA from TOPAZ-1, and KEYNOTE-966 were included: 341 received GemCis + durvalumab, and 533 received GemCis + pembrolizumab. Median age was 64 years, with 50% male in both arms. The median OS was 12.8 months in both groups (p = 0.97) and median PFS was 7.2 versus 6.6months, respectively (p = 0.88). Grade 3/4 events were higher with GemCis + pembrolizumab (78.8%) versus GemCis + durvalumab (65.1%; p < 0.0001), mainly thrombocytopenia, while other toxicities were similar, except abdominal events, which were slightly higher with pembrolizumab (1.88% vs 0.3%; p = 0.0439). Conclusions: In patients with unresectable or metastatic CCA, GemCis with durvalumab or pembrolizumab demonstrates similarity OS and PFS, whereas pembrolizumab was associated with higher incidence of grade 3/4 AEs, predominantly thrombocytopenia, highlighting a differential toxicity profile that may inform first-line treatment selection.