medwireNews: The combination of nivolumab and ipilimumab has antitumor activity in men with metastatic castration-resistant prostate cancer (mCRPC), suggest CheckMate 650 data.
The phase II trial comprised two cohorts, one including 45 chemotherapy-naïve patients who had progressed after at least one prior second-generation hormone therapy and the other consisting of 45 patients who progressed after cytotoxic chemotherapy.
Administration of nivolumab 1 mg/kg alongside ipilimumab 3 mg/kg every 3 weeks for up to four doses elicited an objective response in 25% of the chemotherapy-naïve cohort and 10% of the chemotherapy-treated cohort, over respective median follow-up times of 11.9 and 13.5 months.
Presenting the findings at the 2019 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA, Padmanee Sharma (University of Texas MD Anderson Cancer Center, Houston, USA) highlighted that there were two complete responses in each cohort, and that five of the eight responders in the chemotherapy-naïve cohort and all three responders in the chemotherapy-treated cohort had ongoing responses at data cutoff.
Treatment with nivolumab–ipilimumab also led to prostate-specific antigen (PSA) responses in 17.6% and 10.0% of the chemotherapy-naïve and treated cohorts, respectively, with a corresponding 14.7% and 5.0% achieving undetectable PSA levels (<0.2 ng/mL).
Of note, an exploratory biomarker analysis showed a significant association between response and tumor mutational burden (TMB). Specifically, the objective response rates (ORRs) were significantly higher among participants with high TMB, defined as above the median of 74.5 mutations, than those with low TMB in the chemotherapy-naïve and chemotherapy-treated cohorts, at ORRs of 50.0% versus 9.1% and 50.0% versus 0.0%, respectively.
The team also identified associations between response and PD-L1 expression as well as homologous recombination deficiency, but these did not reach statistical significance, likely due to the small number of patients in the subgroups, postulated Sharma.
With regard to the adverse event (AE) profile, grade 3–5 treatment-related AEs were reported in 42.2% of the chemotherapy-naïve cohort and 53.3% of the chemotherapy-treated cohort, and a respective 33.3% and 35.6% discontinued treatment due to any-grade AEs.
Sharma also noted that just 33.3% of chemotherapy-naïve patients and 24.4% of chemotherapy-treated individuals received all four doses.
Therefore although she believes further study of the combination is warranted in the mCRPC setting, the presenter highlighted that “dose/schedule optimization will be important […] given the number of patients not completing all 4 combination doses and discontinuing study treatment due to toxicity.”
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