Assessment, Analysis, and Discussion
prostatic malignancies, prostate cancer death, tumors, mCRPC, prostate cancer
ADVERSE EVENTS, DISEASE, SOLID TUMORS, SOMATIC MUTATION, EVENTS, TUMOR GROWTH, TUMORS, PROSTATE CANCER
Black men are known to be at higher risk for prostate cancer death.Black patients are continually underrepresented in clinical trials and there are possible racial differences in the molecular profiling of tumors and outcomes of these patients that require further investigation of active therapies in this underrepresented group.At the time of trial design, immune checkpoint inhibitors were being actively testing in several solid tumors and specific data on prostatic malignancies such as the phase III trial KEYNOTE-199 (NCT02787005) was not available. Results from KEYNOTE 199 published in 2019, showed the limited activity of immunotherapy unselected group of mCRPC patients, however distribution by race has not been reported.By the contrary, hyperprogression—defined as a paradoxical boost in tumor growth—has been observed in 4%-29% of solid tumors under treatment with immune checkpoint inhibitors.Our study did not require specific genomic alterations for eligibility, but molecular profiling was required at baseline for all patients. Notably, none of the enrolled patients had known immune-related markers that predict response to immune checkpoint inhibitors. One patient with a pathogenic somatic mutation in the homologous recombination repair gene FANCA had no response to avelumab, yet there is prostate cancer data suggesting other homologous recombination repair gene defects might be predictive of response to immune checkpoint inhibitors, but further validation is required.Critically, we were concerned at the number of serious adverse events experienced by this population, not related to treatment but with progression of their disease. Patients experienced clinical progression with serious events at a much more rapid rate than expected for men of their disease burden and stage of disease. Collectively, our group decided to close the study for safety concerns due to rapid progression of enrolled patients. Further investigation is necessary to confirm these racial differences and better inform the handling of treatment and expectations for Black men with mCRPC.