Olaparib Shows Promise in Multiple Tumor Types

A global phase II study of the PARP inhibitor olaparib (AstraZeneca) for patients with inherited BRCA1 and BRCA2 gene mutations has confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against advanced pancreatic and prostate cancers.

While the numbers of patients in the study with pancreatic and prostate cancer were small (23 and eight respectively), 22% of pancreatic and 50% of prostate cancer patients showed either complete or partial response to olaparib. Additionally, 35% of pancreatic and 25% of prostate cancer patients demonstrated stable disease for at least eight weeks. Overall survival after one year was 41% for patients with pancreatic cancer and 50% for patients with prostate cancer. The results were presented at the American Society for Clinical Oncology 2013 Annual Meeting in Chicago, IL, on June 3.

“We haven't cured anyone, but given where you start with pancreatic cancer, and given the aggressive nature of the prostate cancers that occur in BRCA1/2 carriers, these results are impressive,” says Susan Domchek, MD, director of the Basser Research Center for BRCA at the University of Pennsylvania's Abramson Cancer Center in Philadelphia and the study's senior author. “Prostate and pancreatic cancer are part of BRCA1/2 hereditary breast and ovarian cancer syndrome even if the words aren't in the name.”

Among 193 patients with advanced cisplatin-resistant ovarian cancer, almost all of whom had had at least three chemotherapy treatments, 31% responded to olaparib treatment and 40% showed stable disease for at least eight weeks. One-year survival was 64%.

Thirteen percent of 62 breast cancer patients responded to treatment and 47% showed stable disease for at least eight weeks. Overall survival after one year was 45%.

Patients in the trial reported side effects including mild to moderate nausea and fatigue and some anemia.

Instead of selecting patients with particular cancer-driving mutations, this trial admitted cancer patients with inherited BRCA1/2 mutations regardless of tumor type. BRCA1/2 mutations disable DNA damage repair via homologous recombination. PARP inhibitors disable a second DNA damage repair mechanism known as base excision repair. The loss of both mechanisms can be lethal to tumor cells.

“This study shows that PARP inhibitors remain exciting compounds for BRCA1 and BRCA2 mutation carriers,” says Domchek. “We're looking ahead to planned registration trials.”