title: Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.
abstract: Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC.
  
  
  
  KEYNOTE-012 (ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort.
  
  
  
  Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1-positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks).
  
  
  
  This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium. rnanda@medicine.bsd.uchicago.edu.
authors.forename: Rita
authors.initials: R
authors.lastname: Nanda
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Laura Q M
authors.initials: LQ
authors.lastname: Chow
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Ravit
authors.initials: R
authors.lastname: Geva
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Kumudu
authors.initials: K
authors.lastname: Pathiraja
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Gursel
authors.initials: G
authors.lastname: Aktan
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cheng
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Karantza
authors.affiliation: Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Buisseret
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C582435:pembrolizumab; D007770:L-Lactate Dehydrogenase