Combo olaparib/cediranib slaps down recurrent ovarian cancer
AT THE ASCO ANNUAL MEETING 2014
Key clinical point: Combination olaparib plus cediranib may provide an alternative treatment option for women with recurrent, platinum-sensitive ovarian cancer.
Major finding: Median PFS increased from 9 months with olaparib alone to 17.7 months with the addition of cediranib (hazard ratio, 0.42; P = .005).
Data source: A phase II trial in 90 women with recurrent, platinum-sensitive ovarian cancer.
Disclosures: The study was supported by the National Cancer Institute. Dr. Liu and her coauthors reported no relevant financial disclosures.
CHICAGO – The PARP inhibitor olaparib plus the antiangiogenic cediranib nearly doubled progression-free survival in women with recurrent, platinum-sensitive ovarian cancer in a phase II study.
Median progression-free survival (PFS) was 17.7 months with the combination, compared with 9 months for olaparib alone (hazard ratio, 0.42; P = .005).
Olaparib plus cediranib also significantly increased the overall response rate from 48% to 80% (P = .002), Dr. Joyce F. Liu reported at the annual meeting of the American Society of Clinical Oncology.
This included 5 complete responses and 30 partial responses in the 44 women assigned combination therapy, versus 2 complete and 20 partial responses in the 46 treated with olaparib alone.
"One very exciting possibility about this combination is that it can offer an alternative to standard chemotherapy for women in this setting," she said in an interview. "It offers us more options."
Typically, these patients will receive platinum-based doublets containing carboplatin plus paclitaxel or pegylated liposomal doxorubicin, or gemcitabine, resulting in a median PFS of 8-13 months in phase III studies, said Dr. Liu of Dana-Farber Cancer Institute, Boston, during a press briefing.
Women with platinum-sensitive ovarian cancer are also the patients most likely to be considered for surgical debulking, commented Dr. Don Dizon, director of the Oncology Sexual Health Clinic at Massachusetts General Hospital Cancer Center, Boston. For these women, targeted agents like olaparib and cediranib may provide an alternative if the drugs are able to reset the disease.
Preclinical data have suggested a synergy between PARP (poly-ADP-ribose polymerase) inhibitors and antiangiogenics, and Dr. Liu previously reported phase I data showing an overall response rate of 44% with olaparib plus cediranib in recurrent ovarian cancer (Eur. J. Cancer 2013;49;2972-8).
The open-label, phase II study randomly assigned 90 women (median age, 58 years) with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer to olaparib 400 mg twice daily or cediranib 30 mg daily plus olaparib 200 mg twice daily, all until disease progression by RECIST criteria.
All patients had high-grade serous or endometrioid histology or other high-grade histological subtypes, if a germ-line BRCA mutation was documented.