Celestia Higano, MD
The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is becoming increasingly well defined, with new clinical data emerging to clarify and, in many cases, support the use of poly (ADP-ribose) polymerase (PARP) inhibitors.
DNA repair alterations are present in approximately 25% to 30% of cases of mCRPC, Higano said. These include BRCA1/2, ATM, Fanconi’s anemia, CHEK2, and other gene alterations. Higano stressed that there are 2 ways a patient can develop these alterations: either in tumor DNA, which is observed in about 25% of patients, or in the germ- line setting, which is observed in approximately 12% of patients.
Overall, the study found that 89% of affected individuals harbored a clinically actionable DNA aberration, including 62.7% with aberrations in the androgen receptor, 65% in other cancer-related genes, and 8% with germline alterations.
Targeting PARPs in Cancer
Olaparib (Lynparza), the first PARP inhibitor to gain the FDA’s approval in 2014 with an indication in recurrent ovarian cancer, is being investigated in prostate cancer under a breakthrough therapy designation based on phase II study data. In the trial, olaparib demonstrated high response rates in patients with mCRPC and DNA repair defects.2
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