BRCA-related tumors respond to olaparib

Olaparib, an experimental twice-daily oral cancer drug, produces an overall tumor response rate of 26% in several advanced cancers associated with BRCA1 and BRCA2 mutations, according to new research.

The positive response provides new hope for patients with ovarian, breast, pancreatic, and prostate cancers whose conditions have not responded to standard therapies. Results of the phase II study were published in the Journal of Clinical Oncology (2014; doi:10.1200/JCO.2014.56.2728).

For the majority of patients in the study, olaparib was at least their third different cancer therapy. Based on the new data, the authors say olaparib warrants further investigation in phase III trials. The positive response in metastatic pancreatic cancer patients who had received an average of two prior rounds of chemotherapy is an especially noteworthy finding since therapeutic options for these patients are limited.

The international research team studied nearly 300 patients with inherited BRCA1 and BRCA2 mutations who had advanced cancers that were still growing despite standard treatments. Patients were enrolled and treated at 13 centers around the world. In addition to the 26 overall shrinkage or disappearance rate in tumors following treatment with olaparib, researchers also found no further growth in cancer for at least 8 weeks in 42% of patients.

Overall survival at 1 year following treatment with olaparib was 64% among patient with ovarian cancer (with a median progression-free survival [PFS] of 7 months), 45% among patients with breast cancer (with a median PFS of nearly 4 months), 41% among patients with pancreatic cancer (with a median PFS of nearly 5 months), and 50% among patients with prostate cancer (with a median PFS of more than 7 months).

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

PARP, which is poly (ADP-ribose) polymerase, is used by healthy cells to repair themselves. However, cancer cells also use PARP to repair DNA damage, thus extending their growth and possible lethality. Olaparib selectively binds to and inhibits PARP, potentially preventing it from repairing DNA damage in cancer cells, but not in normal cells. In cancers that also have a mutation in BRCA1 or BRCA2, this may help control the tumor or shrink it.

Side effects were reported for 54% of participants, the most common of which was anemia (17%). Authors suggest the increased incidence of anemia compared to other studies may be due to the study population's longer history of cancer and higher number of prior chemotherapy treatments. Other side effects included fatigue, nausea, and passing episodes of vomiting. Most toxicity could be managed by dose interruption and dose reduction.

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