Maintenance therapy with the novel PARP inhibitor olaparib may fill a gap in the treatment of advanced ovarian cancer by significantly delaying progression of the disease, according to the results of a phase II trial that will be presented at the annual meeting of the American Society of Clinical Oncology.
Olaparib extended median progression-free survival by almost 4 months in women who had a partial or complete response to platinum-based chemotherapy for recurring high-grade serous ovarian cancer – 8.4 months with olaparib vs. 4.8 months with placebo (Hazard Ratio .35, P less than .00001).
"This is a very significant difference – a 65% improvement," said the principal investigator Dr. Jonathan A. Ledermann during a May 18 press briefing, where the results were disclosed.
"This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive, relapsed serous ovarian cancer," noted Dr. Ledermann, a professor of medical oncology at the University College London Cancer Institute.
The results may mean a better quality of life longer for women with this type of ovarian cancer, added Dr. Mark G. Kris, chair of the ASCO Cancer Communications Committee and moderator of the briefing.
This study "fills a previously unmet need for women fighting ovarian cancer ... to lengthen the time that disease is controlled after the complete of successful initial therapy. Generally disease control translates into a normal or near-normal life, which is really the goal of cancer therapy," said Dr. Kris, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City,
The study was sponsored by AstraZeneca, which is developing olaparib. The drug is among the leading candidates in a new class of agents that inhibit the enzyme poly (adenosine diphosphate-ribose) polymerase (PARP), which is involved in DNA repair. As many as half of women with high-grade serous ovarian cancer may have a DNA repair deficiency, and this makes them more susceptible to death of cancer cells by what is called "synthetic lethality" when treated with PARP inhibitors.
The randomized double-blind placebo-controlled phase II study was conducted at 82 sites in 16 countries. Participants had platinum-sensitive, high-grade serous ovarian cancer (the most common subtype), had undergone at least two platinum regimens, and had maintained a partial or complete response following the last platinum regimen.
A total of 136 women were randomized to 400 mg oral olaparib twice daily and 129 women received placebo. The primary end point was progression-free survival based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Dr. Ledermann reported that half the women on olaparib but only 16 on placebo had not relapsed and were still on treatment at the time of the data analysis. Nausea was present in 68% of patients on olaparib, compared with 35% on placebo; fatigue in 49% vs. 38% and vomiting in 32% vs. 14%, respectively.
"The drug was very well-tolerated. ... These side effects were present in patients on placebo, too, because these are patients who have ovarian cancer, but they were more common in the olaparib group," noted Dr. Ledermann.
"Further studies are now being performed to determine the role of olaparib in the routine treatment of ovarian cancer," he said.
Many of the study authors reported either employment with AstraZeneca or other significant financial relationships with the company and several other drugmakers.
Abstracts of studies to be presented during ASCO are posted online at www.asco.org.