Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Emmanuel S. Antonarakis, Josep M. Piulats, Marine Gross-Goupil, Jeffrey Goh, Kristiina Ojamaa, Christopher J. Hoimes, Ulka Vaishampayan, Ranaan Berger, Ahmet Sezer, Tuomo Alanko, Ronald de Wit, Chunde Li, Aurelius Omlin, Giuseppe Procopio, Satoshi Fukasawa, Ken-Ichi Tabata, Se Hoon Park, Susan Feyerabend, Charles G. Drake, Haiyan WuPing Qiu, Jeri Kim, Christian Poehlein, Johann Sebastian de Bono

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Pembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger mCRPC population. METHODS: The phase II KEYNOTE-199 study included three cohorts of patients with mCRPC treated with docetaxel and one or more targeted endocrine therapies. Cohorts 1 and 2 enrolled patients with RECIST-measurable PD-L1-positive and PD-L1-negative disease, respectively. Cohort 3 enrolled patients with bone-predominant disease, regardless of PD-L1 expression. All patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary end point was objective response rate per RECIST v1.1 assessed by central review in cohorts 1 and 2. Secondary end points included disease control rate, duration of response, overall survival (OS), and safety. RESULTS: Two hundred fifty-eight patients were enrolled: 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Objective response rate was 5% (95% CI, 2% to 11%) in cohort 1 and 3% (95% CI, < 1% to 11%) in cohort 2. Median duration of response was not reached (range, 1.9 to ≥ 21.8 months) and 10.6 months (range, 4.4 to 16.8 months), respectively. Disease control rate was 10% in cohort 1, 9% in cohort 2, and 22% in cohort 3. Median OS was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. Treatment-related adverse events occurred in 60% of patients, were of grade 3 to 5 severity in 15%, and led to discontinuation of treatment in 5%. CONCLUSION: Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and OS estimates are encouraging.
Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalJ. Clin. Oncol.
Volume38
Issue number5
DOIs
Publication statusPublished - 2020

Keywords

  • Humans
  • Male
  • Middle Aged
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Biomarkers, Tumor/metabolism
  • B7-H1 Antigen/antagonists & inhibitors/immunology
  • Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects/immunology
  • Antineoplastic Agents, Immunological/administration & dosage/adverse effects/immunology
  • Infusions, Intravenous
  • Prostatic Neoplasms, Castration-Resistant/*drug therapy/immunology/metabolism

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