AstraZeneca's Olaparib Shows Potential In BRCA-Linked Cancers

New research from the Abramson Cancer Center of the University of Pennsylvania shows that olaparib, an investigational twice-daily oral cancer drug, has potential in inducing tumor response rate in several advanced cancers associated with BRCA1 and BRCA2 mutations.

AstraZeneca is developing olaparib as an investigational first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that promotes cancer cell death by interfering with the repair of damaged DNA in tumor cells. PARP is used by both normal cells and cancer cells, however in the case of the latter, PARP can help fix the damage done to cancer cells and extend their survival. The drug selectively binds to PARP in cancer cells while avoiding healthy cells. Cancers that have BRCA mutation may be controlled or halted with olaparib.

Last month, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) backed olaparib for monotherapy and maintenance treatment of advanced ovarian cancer in the EU.

BRCA1 and BRCA2 mutations in women have been shown to increase the risk of breast and ovarian cancer, while BRCA2 mutation in males has been linked to breast, pancreatic, and prostate cancer. An estimated 5 percent of breast cancers and 10 percent of ovarian cancers are linked with an inherited BRCA1 or BRCA2 mutation.

Researchers reported that olaparib achieved an overall tumor response rate of 26 percent in a number of advanced BRCA-related cancers. The drug also inhibited the cancer’s growth for at least eight weeks in 42 patients. Trial results show that olaparib promoted overall survival at one year in 64 percent of patients with ovarian cancer, 45 percent of patients with breast cancer, 41 percent of patients with pancreatic cancer, and 50 percent of patients with prostate cancer.

“By building on previous research, our study offers new hope for patients suffering from cancers caused by inherited BRCA1 and BRCA2 gene mutations. Olaparib was reasonably well tolerated in the current study, even in such a heavily pre-treated population, showing that PARP inhibitors such as olaparib potentially represent a much-needed advanced treatment option,” said Susan Domchek, executive director of the Basser Research Center for BRCA at the University of Pennsylvania’s Abramson Cancer Center.

The Phase 2 study results were published online entitled “Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation” in the Journal of Clinical Oncology. The study was funded by AstraZeneca.