ASCO GU 2020: Pembrolizumab Plus Enzalutamide for Enza-Resistant Metastatic Castration-Resistant Prostate Cancer: KEYNOTE-199 Cohorts 4-5

San Francisco, CA (UroToday.com) During the Rapid Abstract Session, A: Prostate Cancer session at the Annual ASCO GU 2020 meeting in San Francisco, CA, results for KEYNOTE-199 Cohort 4 and 5 were presented by Nicole Graff, MD. Pembrolizumab monotherapy has demonstrated durable activity in PD-L1 positive mCRPC. KEYNOTE-199 is an open-label multicohort phase 2 study of pembrolizumab looking at the antitumor activity and acceptable safety in mCRPC previously treated with next-generation hormone agents and docetaxel.
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Cohort 4 (RECIST-measurable disease) and Cohort 5 (bone-predominant disease) consist of chemotherapy-naive patients with mCRPC treated with enzalutamide plus pembrolizumab after progression with enzalutamide.

Patients with or without prior Abiraterone had clinically meaningful response/benefits to Enzalutamide, followed by disease progression. Patients received Pembrolizumab 200 mg Q3W with the continuation of Enzalutamide for up to 35 cycles or until progression/intolerable toxicity. The primary endpoint was overall response rate (ORR) by RECIST 1.1 per blinded independent central review (Cohort 4). Secondary endpoints were disease control rate (DCR), PSA response rate (≥50% reduction), radiographic progression-free survival (rPFS), overall survival (OS), and safety (Cohort 4 and 5); duration of response (DOR) (Cohort 4).

Dr. Graff then highlighted the results of this study. Of 126 pts (Cohort 4, n= 81; Cohort 5, n=45), 107 discontinued, primarily due to progression. Median follow-up was 15.3 months in Cohort 4 and 19.1 months in Cohort 5.

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ORR (95% CI) for patients with measurable disease was 12% in Cohort 4; DCR for all patients was 51% in Cohort 4 and 51% in Cohort 5. In Cohort 4, 53% experienced a reduction in target lesion size, and 24% experienced greater than 30% reduction. The median duration of response was 6.3 months, and 60% had a durable response greater than six months in Cohort 4.

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PSA decrease from baseline was noted in 40% of the patients, and greater than 50% decrease was seen in 14% of the patients.

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Median rPFS was 4.2 months in Cohort 4 and 4.4 months in Cohort 5. OS in Cohort 5 was 18.8 months.

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Any grade/grade 3-5 treatment-related adverse events occurred in 73%/25% of all patients.  Any grade/grade 3-5 immune-mediated adverse events occurred in 29%/15% of all patients. Two patients in Cohort 4 died of immune-related adverse events (Miller Fisher syndrome and myasthenia gravis). The incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%). All except one patient (grade 3 treated with IV steroids) were treated with oral/topical steroids or had no intervention.

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Dr. Graff concluded her talk by summarizing that the addition of pembrolizumab to enzalutamide following enzalutamide resistance showed modest antitumor activity and durable response in patients with RECIST-measurable and bone-predominant mCRPC. The combination had manageable safety and is being evaluated in a phase 3 trial (KEYNOTE-641, NCT03834493).

Presented by: Julie Nicole Graff, MD, Associate Professor of Medicine, School of Medicine, Oregon Health & Science University, Portland, OR 

Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @shekabhishek, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California.

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