Roxanne Nelson

May 20, 2011

May 20, 2011 — The experimental agent olaparib (AstraZeneca) might have a role to play in ovarian cancer. Results from a phase 2 trial have shown that it significantly prolonged progression-free survival in patients with platinum-sensitive relapsed serous ovarian cancer.

Patients who received olaparib as maintenance therapy achieved a progression-free survival that was nearly 4 months longer than those who received placebo, according to data presented at a press briefing held in advance of the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting.

Median progression-free survival in the olaparib group was 8.4 months, compared with 4.8 months in the placebo group (hazard ratio [HR], 0.35; P < .00001). At the time of the analysis, 50% of olaparib group and 16% of the placebo group were still receiving treatment.

Dr. Jonathan Ledermann

This is the first randomized trial to demonstrate the benefits of a PARP inhibitor as maintenance therapy in platinum-sensitive relapsed serous ovarian cancer, which is the most common form of the disease, explained lead author Jonathan A. Ledermann, MD, professor of medical oncology at UCL Cancer Institute, University College London, United Kingdom.

Dream of Personalized Care

Mark G. Kris, MD, chair of ASCO's Cancer Communications Committee, noted that this trial is significant because "it fills an unmet need" for patients with relapsed ovarian cancer.

Olaparib lengthened the time that the disease could be controlled after the completion of active therapy, he explained, and allowed patients to return to a normal life.

The study also demonstrates the potential of targeted therapy. "That is our dream of personalized care, and this is one example of that dream approaching reality," Dr. Kris said.

Met Primary and Secondary End Points

Olaparib is an investigational poly (ADP ribose) polymerase (PARP) inhibitor that is currently being evaluated in phase 2 clinical studies for the treatment of certain types of ovarian and breast cancer. The results of 2 phase 2 trials, presented at the 2010 ASCO meeting and reported by Medscape Medical News at that time, demonstrated that olaparib produced significant response rates in patients with ovarian or breast cancer associated with BRCA1 or BRCA2 mutations. Responses in these nonrandomized trials were observed even in patients who had undergone 3 previous chemotherapy regimens and who had platinum resistance.

In the current study, Dr. Ledermann and colleagues examined 265 women with high-grade serous ovarian cancer who had received 2 or more previous platinum regimens and who had maintained partial or complete response after their last platinum-containing regimen. The women were randomized to oral olaparib 400 mg (n = 136) or placebo (n = 129).

The primary end point of the study was progression-free survival by RECIST; secondary end points included time to progression by CA-125 (GCIG criteria) or RECIST, overall survival, and safety.

"The study achieved its primary end point," said Dr. Ledermann. "This is a very significant difference — a 65% improvement with a highly significant value of 10–5."

Olaparib also significantly prolonged time to progression by CA-125 or RECIST (HR, 0.35; 95% confidence interval, 0.25 to 0.47; P < .00001). Median time to progression was 8.3 months in the olaparib group and 3.7 months in the placebo group. However, it is not yet known if there is an overall survival benefit; at the time of data cut-off, the data were too immature for analysis.

"The drug was very well tolerated, although there was an increase in 3 particular symptoms: nausea, fatigue, and vomiting," said Dr. Ledermann, pointing out that although these symptoms were seen in the placebo group, they were more common in the olaparib group.

Common adverse events included nausea (68% vs 35%), fatigue (49% vs 38%), vomiting (32% vs 14%), and anemia (17% vs 5%). The majority of events were grade 1 or 2, and the most frequently reported events of grade 3 or higher were fatigue (9 patients) and anemia (7 patients) in the olaparib group, and abdominal pain and fatigue (4 patients each) in the placebo group. A total of 31 patients (23%) in the olaparib group and 9 (7%) in the placebo group had both dose reductions and treatment interruptions.

This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive relapsed serous ovarian cancer, Dr. Ledermann concluded. "Further studies will be performed to determine the role of olaparib in the routine treatment of ovarian cancer."

In a statement, Jane Robertson, MBCHB, MD, medical science director at AstraZeneca, noted that these results are encouraging because "they suggest that olaparib may have a positive effect on progression-free survival in women with serous ovarian cancer, and may be a valuable therapeutic option for this aggressive form of cancer."

The study was funded by AstraZeneca. Dr. Ledermann has disclosed no relevant financial relationships. Several of his coauthors report relationships with AstraZeneca and/or other pharmaceutical companies.

American Society of Clinical Oncology (ASCO) 2011 Annual Meeting: Abstract 5003. To be presented June  4, 2011.

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