Efficacy and safety in advanced intrahepatic cholangiocarcinoma using pembrolizumab combined with lenvatinib and GEMOX: A retrospective analysis of real-world evidence.

e16191 Background: The TOPAZ-1 and KEYNOTE-966 trials have established GemCis and PD1/PDL1 inhibitors as the standard first-line treatments for advanced biliary tract cancer. However, the efficacy and safety of the combination of pembrolizumab combined with lenvatinib and GEMOX in advanced intrahepatic cholangiocarcinoma (ICC) patients remains uncertain. Methods: In this retrospective study, consecutive patients with unresectable, locally advanced ICC who had received the pembrolizumab combined with lenvatinib and GEMOX were enrolled. Eligible participants had pathologically confirmed advanced ICC. Patients were received the standard dose of pembrolizumab in combination with GEMOX, while the dose of lenvatinib was 4mg. The primary efficacy endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), which were evaluated in accordance with the mRECIST criteria. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: A total of 71 eligible patients were enrolled from October 2021 to September 2024. By the data cut-off in January 2025, the median follow-up time was 8.8 months. It was observed that patients who suffered from recurrence after radical hepatectomy had shorter OS compared to those who had not (11.8, 95%CI 3.2-20.3 months v.s. 21.3, 95%CI 12.4-30.1months, p = 0.024). In the total cohort, the estimated median OS was17.3 (95% CI 10.3-24.3) months, while the median PFS was 7.1 (95% CI 4.7 - 9.5) months. ORR and DCR were 38.0% and 78.9%, respectively. Among them, 40 patients received the combined therapy as first-line systemic therapy and demonstrated a better ORR (55.0%) and DCR (87.5%). Nearly all patients experienced AEs. G3/4 AE within 6 months after the initiation of combined therapy occurred in 24 (33.8%) patients. Six patients underwent hepatectomy after successful conversion therapy. Conclusions: The combination of pembrolizumab combined with lenvatinib and GEMOX shows promise as a first-line regimen for advanced ICC, with generally acceptable safety and efficacy. However, further prospective studies with larger sample sizes are needed to confirm these findings. Outcomes. Outcomes Patients received pembrolizumab combined with lenvatinib and GEMOX(N = 71) Patients received pembrolizumab combined with lenvatinib and GEMOX as first-line treatment (N = 40) CR/PR/SD/PD 1/26/29/15 1/21/13/5 ORR 38.0% 57.6% DCR 78.9% 87.9% OS(m) 17.3(10.3-24.3) NR 3/6/9-month OS rate 94.1%/84.6%/82.1% 94.8%/87.8%/83.2% PFS(m) 7.1(4.7-9.5) 8.47(6.4-10.5) 3/6/9month PFS rate 87.2%/54.6%/37.6% 90.0%/58.9%/41.9%