Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer

被引:257
|
作者
Rugo, Hope S. [1 ]
Delord, Jean-Pierre [2 ]
Im, Seock-Ah [3 ]
Ott, Patrick A. [4 ]
Piha-Paul, Sarina A. [5 ]
Bedard, Philippe L. [6 ]
Sachdev, Jasgit [7 ]
Le Tourneau, Christophe [8 ,9 ,10 ,11 ]
van Brummelen, Emilie M. J. [12 ]
Varga, Andrea [13 ]
Salgado, Roberto [14 ]
Loi, Sherene [14 ]
Saraf, Sanatan [15 ]
Pietrangelo, Dina [15 ]
Karantza, Vassiliki [15 ]
Tan, Antoinette R. [16 ,17 ]
机构
[1] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA
[2] Inst Claudius Regaud, Dept Med Oncol, Oncolpole Toulouse, France
[3] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Internal Med,Canc Res Inst, Seoul, South Korea
[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA
[6] UHN Princess Margaret Canc Ctr, Div Med Oncol, Toronto, ON, Canada
[7] Scottsdale Healthcare Shea Med Ctr, Breast & GYN Early Trials Program, Scottsdale, AZ USA
[8] Inst Curie, Dept Drug Dev & Innovat, Paris, France
[9] Inst Curie, Dept Drug Dev & Innovat, St Cloud, France
[10] INSERM, Res Unit U900, St Cloud, France
[11] Versailles St Quentin en Yvelines Univ, Montigny Le Bretonneux, France
[12] Netherlands Canc Inst, Dept Clin Pharmacol, Amsterdam, Netherlands
[13] Gustave Roussy, Drug Dev Dept, Villejuif, France
[14] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
[15] Merck & Co Inc, Dept Clin Oncol, Kenilworth, NJ USA
[16] Rutgers Canc Inst New Jersey, Div Med Oncol, Dept Med, New Brunswick, NJ USA
[17] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA
关键词
1ST-LINE THERAPY; OPEN-LABEL; PHASE-2; PALBOCICLIB; IPILIMUMAB; EXPRESSION; MULTICENTER; MONOTHERAPY; LETROZOLE; EFFICACY;
D O I
10.1158/1078-0432.CCR-17-3452
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: We investigated the safety and antitumor activity of the anti-programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2(-)) advanced breast cancer with programmed death ligand 1-positive (PD-L1-positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. Patients and Methods: Patients with ER+/HER2(-)advanced breast cancer with PD-L1-positive tumors (combined positive score >= 1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review. Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3-15). Median follow-up was 9.7 months (range, 0.7-31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%-31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for >= 24 weeks]) was 20% (95% CI, 7-41). Median duration of response was 12.0 months (range, 7.4-15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred. Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1-positive, ER+/HER2(-) breast cancer. (C) 2018 AACR
引用
收藏
页码:2804 / 2811
页数:8
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