Abstract ▼ AI-Helper

Background: For patients with advanced BTC, standard chemotherapy has limited benefit and no molecular targeted agents have been approved. Pembrolizumab is an anti PD-1 immune checkpoint inhibitor which has shown modest activity for advanced BTC patients in prior single-arm phase I/II studies. Consi...

Background: For patients with advanced BTC, standard chemotherapy has limited benefit and no molecular targeted agents have been approved. Pembrolizumab is an anti PD-1 immune checkpoint inhibitor which has shown modest activity for advanced BTC patients in prior single-arm phase I/II studies. Considering the heterogeneity of BTC, more data are needed to evaluate the clinical outcomes of pembrolizumab in unresectable or metastatic BTC.
Methods: In this prospective cohort study, programmed death ligand-1 (PD-L1)-positive BTC patients who progressed on 1st-line gemcitabine plus cisplatin were enrolled. Pembrolizumab was given at a fixed dose of 200 mg intravenously, every 3 weeks.
Results: Between May 2018 and February 2019, 40 patients were enrolled. The median age was 61 years (range, 41–76), and 23 (57.5%) patients were male. Intrahepatic cholangiocarcinoma was the most common type (n=20, 50%), followed by gallbladder cancer (n=12, 30%), and extrahepatic cholangiocarcinoma (n=8, 20%). Pembrolizumab was given as 2nd-line (47.5%) or ≥ 3rd-line therapy (52.5%). The objective response rate was 10% by RECIST v1.1. and the median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0–3.0) and 4.3 months (95% CI, 3.5–5.1), respectively, and objective response was significantly associated with PFS (p<0.001) and OS (p=0.001). Tumor proportion score ≥50% was significantly associated with higher response rates, when including the response after pseudoprogression (vs. <50%; 37.5% vs. 6.5%; p=0.049). No patients experienced grade 3–5 adverse events, and no adverse event-related treatment delays or interruptions were reported.
Conclusion: Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1-positive advanced BTC patients. In patients who showed objective response, durable response could be achieved.

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