Olaparib Treatment Yields Promising Response Rates in Patients With BRCA Mutation–Associated Cancers
Olaparib, an experimental twice-daily oral cancer drug, produced an overall tumor response rate of 26% in several advanced cancers associated with BRCA1 and BRCA2 mutations, according to a phase II study reported by Kaufman et al in the Journal of Clinical Oncology. The positive response provides new hope for patients with ovarian, breast, pancreatic, and prostate cancers whose conditions have not responded to standard therapies.
Poly (ADP-ribose) polymerase (PARP) 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.
BRCA1 and BRCA2 mutations in women increase the risk of several cancers, including breast and ovarian, while in males the BRCA2 mutation in particular has been tied to breast, prostate, and pancreatic cancer.
Study Details
The majority of study participants had received at least two prior lines of treatment before receiving olaparib. 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% tumor response rate 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 ovarian cancer patients (with a median progression-free survival of 7 months); 45% among breast cancer patients (with a median progression-free survival of nearly 4 months); 41% among pancreatic cancer patients (with a median progression-free survival of nearly 5 months); and 50% among prostate cancer patients (with a median progression-free survival of more than 7 months).
Potential Treatment Option for Advanced Cancers
“By building on previous research, our study offers new hope for patients suffering from cancers caused by inherited BRCA1 and BRCA2 gene mutations,” said Susan Domchek, MD, Executive Director of the Basser Research Center for BRCA at the University of Pennsylvania’s Abramson Cancer Center, and senior author on the study. “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.”
Side effects were reported for 54% of participants, the most common of which was anemia (17%). The authors suggested that 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.
Dr. Domchek is the corresponding author for the Journal of Clinical Oncology article.
The study was sponsored by AstraZeneca. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
