TY - JOUR
T1 - Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer
T2 - Multicohort, open-label phase II KEYNOTE-199 study
AU - Antonarakis, Emmanuel S.
AU - Piulats, Josep M.
AU - Gross-Goupil, Marine
AU - Goh, Jeffrey
AU - Ojamaa, Kristiina
AU - Hoimes, Christopher J.
AU - Vaishampayan, Ulka
AU - Berger, Ranaan
AU - Sezer, Ahmet
AU - Alanko, Tuomo
AU - de Wit, Ronald
AU - Li, Chunde
AU - Omlin, Aurelius
AU - Procopio, Giuseppe
AU - Fukasawa, Satoshi
AU - Tabata, Ken ichi
AU - Park, Se Hoon
AU - Feyerabend, Susan
AU - Drake, Charles G.
AU - Wu, Haiyan
AU - Qiu, Ping
AU - Kim, Jeri
AU - Poehlein, Christian
AU - de Bono, Johann Sebastian
N1 - Publisher Copyright:
© 2019 by American Society of Clinical Oncology
PY - 2020/2/10
Y1 - 2020/2/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.19.01638
DO - 10.1200/JCO.19.01638
M3 - Article
C2 - 31774688
AN - SCOPUS:85078549076
SN - 0732-183X
VL - 38
SP - 395
EP - 405
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 5
ER -