(UroToday.com) Poly (ADP-ribose) polymerase inhibitors provide clinical benefit across multiple cancers with germline or somatic alterations in the BRCA1 and BRCA2 genes, as well as other select genes within the homologous recombination DNA repair pathway. The PARP inhibitors olaparib and rucaparib are approved for use in metastatic castration-resistant prostate cancer (mCRPC) in patients harboring certain genomic alterations in the DNA damage repair pathway. Talazoparib is another PARP inhibitor, which in a phase 2 study (TALAPRO-1) demonstrated anti-tumor activity in men with mCRPC harboring alterations in homologous recombination repair. Interestingly, androgen pathway inhibitors such as enzalutamide have been shown to downregulate the expression of homologous recombination repair genes, resulting in a BRCA-like phenotype in cancer cells. To test the hypothesis that the addition of PARP inhibition to enzalutamide can improve clinical outcomes of enzalutamide alone, Dr. Aggarwal and colleagues presented the TALAPRO-2 trial.

X