(UroToday.com) In this presentation, Dr. Daniel Petrylak discussed results from the final analysis of CheckMate 9KD Cohort A2. This single-arm study evaluated the clinical activity of nivolumab plus rucaparib in men with metastatic castration-resistant prostate cancer (mCRPC) previously untreated with chemotherapy or PARP inhibitor. Patients eligible for Cohort A2 were not candidates for or refused chemotherapy. Eligible patients received nivolumab 480 mg every 4 weeks and rucaparib 600 mg BID. The co-primary endpoints were overall response rate (ORR) and PSA response rate.
71 men were treated on Cohort A2. Median age was 74, median PSA was 38 ng/ml, and 24% had visceral metastases. Approximately half (48%) of men were homologous recombination deficient (HRD). At the time of the final analysis, the median follow-up was 17.5 months. The median duration of treatment was 4.6 months of Nivolumab and 5.5 months for rucaparib. At the time of analysis, 92% of men had discontinued treatment. The most common reasons for treatment discontinuation were disease progression (61%) and study drug toxicity (11%).
The confirmed ORR was 15.4% in all patients. There was a notable difference in the ORR rate by HRD status: 5.3% in HRD-negative or not evaluable, 25.0% in HRD-positive patients, and 33.3% in patients harboring deleterious BRCA1/2 alterations. The waterfall plots of change from baseline in target lesions and PSA further reflect that responders are enriched for patients with BRCA1/2 alterations. The median duration of response was 7.1 months (95% CI 3.8-not estimable) with a median time to PSA progression of 3.5 months (95% CI 2.8-6.2)
Evaluation of Kaplan-Meier curves for radiographic progression-free survival (rPFS) and overall survival (OS) show similar trends. Median rPFS in the overall cohort was 8.1 months. When split into subgroups by HRD status, rPFS was 5.6 months for HRD-negative and 10.9 months for HRD-positive patients. Likewise, median OS was 20.2 months in the overall cohort, 19.0 months in HRD-negative patients, and 22.7 months in HRD-positive patients.
The combination of nivolumab plus rucaparib led to expected adverse event rates. Any grade treatment-related adverse events (TRAE) led to discontinuation in 23.9% of patients. All other TRAEs Grade 3-4 TRAEs lead to discontinuation in 15.5% of patients. The most common Grade 3-4 TRAEs were anemia (14.1%), increased ALT (12.7), and increase AST (7.0%). All other Grade 3-4 TRAES occurred in less than 5% of patients. There were no treatment-related deaths reported.
Dr. Petrylak concluded that nivolumab plus rucaparib showed clinically efficacy in HRD-positive, chemotherapy-naïve men with mCRPC with notable activity in patients harboring BRCA1/2 alterations. There were no new safety signals for the combination. Longer follow-up is needed to better characterize the clinical benefit of adding nivolumab to rucaparib in men with HRD-positive, chemotherapy-naïve men with mCRPC.
Presented by: Daniel P. Petrylak, MD, Professor of Medicine (Medical Oncology) and of Urology; Co-Leader, Cancer Signaling Networks, Yale Cancer Center
Written by: Jacob Berchuck, MD, Genitourinary Medical Oncologist, Dana-Farber Cancer Institute (Twitter: @jberchuck) during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.