Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study.

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.

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.

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%.

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Nov 27 [Epub ahead of print]

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 Wu, Ping Qiu, Jeri Kim, Christian Poehlein, Johann Sebastian de Bono

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD., Catalan Cancer Institute, Bellvitge Biomedical Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Hospitalet de Llobregat, Barcelona, Spain., Institut Bergonié, Bordeaux, France., Royal Brisbane and Women's Hospital, Herston, QLD, Australia., East Tallinn Central Hospital, Tallinn, Estonia., Case Comprehensive Cancer Center at University Hospitals Seidman Cancer Center, Cleveland, OH., Karmanos Cancer Institute, Wayne State University, Detroit, MI., Chaim Sheba Medical Center, Tel Hashomer, Israel., Başkent University Hospital Adana, Adana, Turkey., Docrates Cancer Center, Helsinki, Finland., Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Karolinska Institutet, Stockholm, Sweden., Cantonal Hospital St Gallen, University of Bern, Bern, Switzerland., Fondazione Istituto Nazionale Tumori, Milan, Italy., Chiba Cancer Center, Chiba, Japan., Kitasato University, Kanagawa, Japan., Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea., Studienpraxis Urologie, Nürtingen, Germany., New York Presbyterian/Columbia University Medical Center, New York, NY., MSD China, Beijing, China., Merck & Co, Kenilworth, NJ., The Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom.

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