The GALAHAD trial showed that people with metastatic castration-resistant prostate cancer (mCRPC) and inherited BRCA mutations had improved survival when treated with the PARP inhibitor, niraparib.
mCRPC does not respond to the hormone treatments that are common for metastatic prostate cancer. Instead, it grows despite treatment and causes death more often than other forms. Researchers are trying to develop more effective approaches to treat mCRPC.
One approach is based on a feature common in some mCRPC tumors. About one-fourth of mCRPC tumors have a mutation that disrupts repair of DNA damage. These include inherited mutations in the BRCA1, BRCA2, PALB2, BRIP1 genes among others. PARP inhibitors were developed to treat tumors like these with defective DNA repair.
The PARP inhibitor niraparib is approved to treat people with certain ovarian, fallopian tube or primary peritoneal cancers, with and without BRCA gene defects. Niraparib is not approved yet for treating prostate cancer.
The GALAHAD study looked whether niraparib improved outcomes for people with mCRPC. Participants with a mutation in BRCA1 or BRCA2 had better survival with niraparib treatment than people without a BRCA mutation. This benefited people with an inherited BRCA1 or BRCA2 mutation as well as those with a mutation only in their tumor. Most people had some side effects from niraparib, but these were similar to previous reports.
Bottomline: Niraparib is a promising treatment for mCRPC, particularly for people with BRCA1 or BRCA2 mutations.