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


Emmanuel S Antonarakis 1, Josep M Piulats 2, Marine Gross-Goupil 3, Jeffrey Goh 4 5, Kristiina Ojamaa 6, Christopher J Hoimes 7, Ulka Vaishampayan 8, Ranaan Berger 9, Ahmet Sezer 10, Tuomo Alanko 11, Ronald de Wit 12, Chunde Li 13, Aurelius Omlin 14, Giuseppe Procopio 15, Satoshi Fukasawa 16, Ken-Ichi Tabata 17, Se Hoon Park 18, Susan Feyerabend 19, Charles G Drake 20, Haiyan Wu 21, Ping Qiu 22, Jeri Kim 22, Christian Poehlein 22, Johann Sebastian de Bono

Main idea: Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant metastatic castration-resistant prostate cancer previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and overall survival estimates are encouraging.


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%.


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