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.
International journal of cancer. 2020 May 02 [Epub ahead of print]
Sarina A Piha-Paul, Do-Youn Oh, Makoto Ueno, David Malka, Hyun Cheol Chung, Adnan Nagrial, Robin K Kelley, Willeke Ros, Antoine Italiano, Kazuhiko Nakagawa, Hope S Rugo, Filippo de Braud, Andrea Iolanda Varga, Aaron Hansen, Hui Wang, Suba Krishnan, Kevin G Norwood, Toshihiko Doi
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan., Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Blacktown Cancer and Haematology Centre, Blacktown Hospital and University of Sydney, Sydney, New South Wales, Australia., Division of Hematology/Oncology, University of California San Francisco, San Francisco, California, USA., Division of Pharmacology, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, Netherlands., Early phase Trials and Sarcoma Units, Institut Bergonié, Bordeaux, France., Department of Medical Oncology, Kindai University Hospital, Osaka, Japan., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA., Department of Oncology and Hemato-Oncology, University of Milan and Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy., Department of Drug Development, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Biostatistical and Research Decision Sciences, Merck & Co., Inc., Kenilworth, New Jersey, USA., Oncology Late Development, Merck & Co., Inc., Kenilworth, New Jersey, USA., Department of Experimental Therapeutics/Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.