572 Background: Cholangiocarcinoma (CCA) is a rare, and aggressive malignancy with limited treatment options, where gemcitabine plus cisplatin (GemCis) has long been the first-line standard. Immunotherapy (IO) has shown promise across cancer types, but its benefit remains uncertain. This meta-analysis assesses the efficacy and safety of IO-based regimens compared with GemCis alone in phase III trials. Methods: For this meta-analysis, we searched PubMed, Embase, Scopus, Google Scholar for studies published from 2023. Eligible studies included randomized clinical trials evaluating ICPIs plus GemCis versus GemCis plus placebo as first-line treatment for unresectable or metastatic CCA. The primary outcome was OS, and the secondary outcomes included progression-free survival (PFS) and adverse events. For studies presenting Kaplan-Meier curves, individual patient data (IPD) tool was used to reconstruct the data for outcome calculations. Results: A total of 1,754 patients with Unresectable or metastatic CCA from TOPAZ-1, and KEYNOTE-966 were included: 880 received GemCis + placebo, 533 received GemCis + pembrolizumab, and 341 received GemCis + durvalumab; median age was 63-64 years, 50% male. The meta-analysis showed that median OS was 11.2 months with GemCis alone, compared with 12.9 months for GemCis+ durvalumab and 12.8 months for GemCis + pembrolizumab groups (p<0.001); median PFS was 5.7, 7.2, and 6.6 months, respectively (p<0.011).Grade 3/4 events were highest with GemCis + pembrolizumab (78.8%) vs GemCis + placebo (68.6%) and GemCis + durvalumab (65.1%; p=0.0001), mainly thrombocytopenia, asthenia, and vomiting. Other toxicities showed no significant differences. Conclusions: Adding IO to GemCis in unresectable or metastatic CCA modestly improved OS and PFS versus GemCis alone, particularly GemCis+ durvalumab.
Al-Najjar et al. (Sat,) studied this question.