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

来源：

INTERNATIONAL JOURNAL OF CANCER | 2020年 / 147卷 / 08期

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

页码：2190 / 2198

页数：9

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