The Study: Its prevalence appears enriched among men with metastatic castration resistant prostate cancer (mCRPC), and such mutations may have prognostic and therapeutic significance. PROREPAIR-B was a large, Spanish prospective study designed to determine the prevalence and significance of germline mutations in DNA repair genes. This non-selected cohort of men were tested at diagnosis of mCRPC for deleterious mutations in BRCA1, BRCA2, ATM, and PALB2 and followed for a primary endpoint of cancer-specific survival. Of over 400 patients enrolled, only 6% carried germline mutations in BRCA or ATM (and none in PALB2), though over 16% had mutations in a broader testing of >100 DNA repair genes. It’s important to note here that this is a much different population from many American studies where such founder mutations account for a significant proportion of cancers. Though numbers were small, median cancer-specific survival was quite a bit better among non-carriers (33 months) than carriers (23 months) and was particularly poor among BRCA2-carriers (17 months). While exploratory, there was a noted interaction between BRCA2-mutations and treatment type where such men with treated with enzalutamide had better survival than those treated with docetaxel.
Bottom Line: This prospective study confirms the enriched prevalence of DNA repair mutations in men with mCRPC, which portends worse cancer outcomes and may respond better to enzalutamide. | Castro, J Clin Oncol 2019