The PARP inhibitor olaparib has already shown promise in treating patients with ovarian and breast cancers who have BRCA1 or BRCA2 germline mutations. Now, a study reported in the Journal of Clinical Oncology has found that the drug also shrinks prostate and pancreatic tumors in people who have these mutations.
BRCA mutations disable DNA damage repair via homologous recombination. PARP inhibitors knock out a second repair mechanism called base excision repair. The loss of both can kill tumor cells.
Although no PARP inhibitor is approved for use in the United States, olaparib (Lynparza; AstraZeneca) has been recommended for approval in Europe for advanced ovarian cancer. Researchers are, however, still trying to determine whether patients with other BRCA-associated cancers might respond to the drug. Few studies have measured olaparib’s effects in patients with BRCA mutations and prostate or pancreatic cancer, or in patients with BRCA mutations whose ovarian or breast tumors resist first-line treatments.
Susan Domchek, MD, of the University of Pennsylvania in Philadelphia, and colleagues tested olaparib in 298 patients who carried germline BRCA mutations and had already received an average of four prior drug regimens. Most of the patients in this phase II trial had ovarian, breast, prostate, or pancreatic cancers.