Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE‐158 and KEYNOTE‐028 studies

• Published in: International journal of cancer Vol. 147; no. 8; pp. 2190 - 2198
• Main Authors: Piha‐Paul, Sarina A., Oh, Do‐Youn, Ueno, Makoto, Malka, David, Chung, Hyun Cheol, Nagrial, Adnan, Kelley, Robin K., Ros, Willeke, Italiano, Antoine, Nakagawa, Kazuhiko, Rugo, Hope S., Braud, Filippo, Varga, Andrea Iolanda, Hansen, Aaron, Wang, Hui, Krishnan, Suba, Norwood, Kevin G., Doi, Toshihiko
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.10.2020; Wiley Subscription Services, Inc
• Subjects: Aged; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Antitumor activity; B7-H1 Antigen - metabolism; Biliary tract; biliary tract cancer; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - metabolism; Cancer; Cholangiocarcinoma; Female; Humans; Immunotherapy; Male; Medical research; Monoclonal antibodies; MSI‐H; Oncology; PD-L1 protein; PD‐L1; Pembrolizumab; Renal failure; Response Evaluation Criteria in Solid Tumors; Solid tumors; Targeted cancer therapy; Toxicity; Tumors; biliary tract cancer; PD-L1; pembrolizumab; MSI-H
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.33013

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE‐158 (NCT02628067; phase 2) and KEYNOTE‐028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD‐L1)‐positive tumors were required for eligibility in KEYNOTE‐028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE‐158) or 10 mg/kg every two weeks (KEYNOTE‐028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE‐158 enrolled 104 patients and KEYNOTE‐028 enrolled 24 patients. Median (range) follow‐up was 7.5 months (0.6‐34.3) in KEYNOTE‐158 and 5.7 months (0.6‐55.4) in KEYNOTE‐028. In KEYNOTE‐158, ORR was 5.8% (6/104; 95% CI, 2.1%‐12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2‐26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5‐9.6) and 2.0 (1.9‐2.1) months. Among PD‐L1‐expressers (n = 61) and PD‐L1‐nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE‐028, ORR was 13.0% (3/23; 95% CI, 2.8%‐33.6%); median DOR was NR (range, 21.5‐53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1‐9.8) and 1.8 (1.4‐3.1) months. Grade 3 to 5 treatment‐related adverse events occurred in 13.5% of patients in KEYNOTE‐158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE‐028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD‐L1 expression, and has manageable toxicity. What's new? Biliary tract cancer is usually diagnosed at a late stage and has a terrible prognosis, and few treatment options are available. Here, the authors present results from 2 clinical trials that evaluated pembrolizumab, a monoclonal antibody that binds to the programmed death 1 receptor (PD‐1) in patients with advanced BTC. Six to 13% of patients had an objective response. Among those who had a response, this was long‐lasting. All were of at least 6 months duration, with one lasting more than 4 years.