Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

• Published in: Cancer research and treatment 2020, 52(2), , pp.594-603
• Main Authors: Kang, Junho, Jeong, Jae Ho, Hwang, Hee-Sang, Lee, Sang Soo, Park, Do Hyun, Oh, Dong Wook, Song, Tae Jun, Kim, Ki-Hun, Hwang, Shin, Hwang, Dae Wook, Kim, Song Cheol, Park, Jin-Hong, Hong, Seung-Mo, Kim, Kyu-Pyo, Ryoo, Baek-Yeol, Yoo, Changhoon
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Bile Duct Neoplasms - drug therapy; Biomarkers - blood; Cohort Studies; Female; Humans; Male; Middle Aged; Original; Progression-Free Survival; Prospective Studies; 의학일반
• ISSN: 1598-2998; 2005-9256
• DOI: 10.4143/crt.2019.493

The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated. In this prospective cohort study, programmed death ligand-1 (PD-L1)-positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks. Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and 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 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049). Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1-positive BTC patients. In patients who showed objective response, durable response could be achieved.