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

• Published in: Clinical cancer research Vol. 24; no. 12; pp. 2804 - 2811
• Main Authors: Rugo, Hope S., Delord, Jean-Pierre, Im, Seock-Ah, Ott, Patrick A., Piha-Paul, Sarina A., Bedard, Philippe L., Sachdev, Jasgit, Tourneau, Christophe Le, van Brummelen, Emilie M.J., Varga, Andrea, Salgado, Roberto, Loi, Sherene, Saraf, Sanatan, Pietrangelo, Dina, Karantza, Vassiliki, Tan, Antoinette R.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.06.2018
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Anticancer properties; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Antitumor activity; B7-H1 Antigen - antagonists & inhibitors; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Epidermal growth factor; ErbB-2 protein; Estrogen receptors; Estrogens; Fatigue; Female; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Middle Aged; Monoclonal antibodies; Nausea; Neoplasm Grading; Neoplasm Staging; Patients; PD-1 protein; PD-L1 protein; Pembrolizumab; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Safety; Solid tumors; Targeted cancer therapy; Toxicity; Tumors
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-3452

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. Clin Cancer Res; 24(12); 2804–11. ©2018 AACR.