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

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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243 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2190-2198
Number of pages9
JournalInternational Journal of Cancer
Issue number8
Publication statusPublished - 2020 Oct 15

Bibliographical note

Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). We thank the patients and their families and caregivers for participating in our study, along with all investigators and site personnel. Additional statistical support was provided by Lei Xu, PhD, and Chao Gao, PhD (former employee), and additional study support was provided by Melanie Leiby, PhD, of Merck & Co., Inc., Kenilworth, NJ, USA, and funded by MSD. Medical writing assistance was provided by Michael J. Theisen of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company. This assistance was funded by MSD.

Publisher Copyright:
© 2020 UICC

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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