Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies |
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| Authors: | 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 |
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| Institution: | 1. Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;2. Department of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;3. Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan;4. Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France;5. Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea;6. Blacktown Cancer and Haematology Centre, Blacktown Hospital and University of Sydney, Sydney, New South Wales, Australia;7. Division of Hematology/Oncology, University of California San Francisco, San Francisco, California, USA;8. Division of Pharmacology, Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, Netherlands;9. Early phase Trials and Sarcoma Units, Institut Bergonié, Bordeaux, France;10. Department of Medical Oncology, Kindai University Hospital, Osaka, Japan;11. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA;12. Department of Oncology and Hemato-Oncology, University of Milan and Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;13. Department of Drug Development, Gustave Roussy, Université Paris-Saclay, Villejuif, France;14. Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada;15. Biostatistical and Research Decision Sciences, Merck & Co., Inc., Kenilworth, New Jersey, USA;16. Oncology Late Development, Merck & Co., Inc., Kenilworth, New Jersey, USA;17. Department of Experimental Therapeutics/Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan |
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| Abstract: | 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. |
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| Keywords: | biliary tract cancer MSI-H PD-L1 pembrolizumab |
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