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

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 38 Issue 5 Pg. 395-405 (02 10 2020) ISSN: 1527-7755 [Electronic] United States
• PMID: 31774688 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• pembrolizumab

Topics

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