PARP Inhibitor Prolongs Progression-Free Survival in Ovarian Cancer

Online First - Conference Correspondent
Audrey Andrews

CHICAGO—The oral poly (ADP-ribose) polymerase (PARP) inhibitor olaparib delayed ovarian cancer recurrence by 4 months when given as maintenance therapy to patients with platinum-sensitive relapsed ovarian cancer, in an international study reported at the 2011 annual meeting of the American Society of Clinical Oncology by Jonathan Ledermann, MD, professor of medical oncology, University College London, United Kingdom.

 

“Olaparib significantly prolonged progression-free survival by nearly 4 months on average, compared with placebo. This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive relapsed serous ovarian cancer,” Ledermann said.

 

Olaparib targets DNA repair weakness in tumors by inhibiting base excision repair in a process known as homologous repair deficiency, which is observed in about 50% of women with ovarian cancer.

 

This study was an international phase 2, randomized, placebo-controlled study of olaparib (400 mg twice daily) as maintenance therapy in 265 patients who had previously responded to at least 2 platinum-based regimens but had relapsed.

 

Disease progression occurred in 44% of the olaparib arm compared with 72% of the placebo arm; median progression-free survival was 8.4 months compared with 4.8 months, respectively. This translated into a 65% reduction in risk of progression that was highly significant (P <.00001).

 

“Our progression-free survival difference was very impressive and better than we anticipated,” Ledermann commented at a press briefing. At the time of analysis, 50% of patients receiving olaparib were still on-treatment, compared with only 16% of the placebo patients.

“Olaparib was well tolerated, and toxicities were consistent with those seen in previous studies,” he said, “although we saw an increase in 3 side effects with the drug.” These included nausea (68% vs 35%), fatigue (49% vs 38%), and vomiting (32% vs 14%).

 

Further studies will help determine the drug’s role in the routine treatment of ovarian cancer, he added.

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Last modified: May 21, 2015