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

被引:402
作者
Piha-Paul, Sarina A. [1 ]
Oh, Do-Youn [2 ,3 ]
Ueno, Makoto [4 ]
Malka, David [5 ]
Chung, Hyun Cheol [6 ]
Nagrial, Adnan [7 ,8 ]
Kelley, Robin K. [9 ]
Ros, Willeke [10 ]
Italiano, Antoine [11 ,12 ]
Nakagawa, Kazuhiko [13 ]
Rugo, Hope S. [14 ]
de Braud, Filippo [15 ,16 ]
Varga, Andrea Iolanda [17 ]
Hansen, Aaron [18 ]
Wang, Hui [19 ]
Krishnan, Suba [20 ]
Norwood, Kevin G. [20 ]
Doi, Toshihiko [21 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA
[2] Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea
[3] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
[4] Kanagawa Canc Ctr, Hepatobiliary & Pancreat Med Oncol Div, Dept Gastroenterol, Yokohama, Kanagawa, Japan
[5] Univ Paris Saclay, Dept Med Oncol, Gustave Roussy, Villejuif, France
[6] Yonsei Univ, Coll Med, Dept Med Oncol, Yonsei Canc Ctr, Seoul, South Korea
[7] Blacktown Hosp, Blacktown Canc & Haematol Ctr, Sydney, NSW, Australia
[8] Univ Sydney, Sydney, NSW, Australia
[9] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA
[10] Antoni van Leeuwenhoek Ziekenhuis, Div Pharmacol, Amsterdam, Netherlands
[11] Inst Bergonie, Early Phase Trials Unit, Bordeaux, France
[12] Inst Bergonie, Sarcoma Unit, Bordeaux, France
[13] Kindai Univ Hosp, Dept Med Oncol, Osaka, Japan
[14] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
[15] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy
[16] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol & Hematol, Milan, Italy
[17] Univ Paris Saclay, Dept Drug Dev, Gustave Roussy, Villejuif, France
[18] Princess Margaret Canc Ctr, Div Med Oncol, Toronto, ON, Canada
[19] Merck & Co Inc, Biostat & Res Decis Sci, Kenilworth, NJ USA
[20] Merck & Co Inc, Oncol Late Dev, Kenilworth, NJ USA
[21] Natl Canc Ctr Hosp East, Dept Expt Therapeut Gastrointestinal Oncol, Kashiwa, Chiba, Japan
关键词
biliary tract cancer; MSI-H; PD-L1; pembrolizumab; TRACT CANCER; EXPRESSION; CRITERIA; PROFILE; TUMORS;
D O I
10.1002/ijc.33013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2190 / 2198
页数:9
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