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Adding PARP Inhibitor to Maintenance Regimen for Ovarian Cancer Enhances PFS, Study Shows

Jaime Rosenberg
According to the findings, adding poly (ADP ribose) polymerase (PARP) inhibitor olaparib to bevacizumab extended progression-free survival (PFS) in women with advanced stage ovarian cancer, with or without a BRCA mutation.
 
More women benefit from a more intensive maintenance regimen for ovarian cancer that includes a targeted therapy, according to study findings coming out of the European Society for Medical Oncology Congress 2019 being held September 27-October 1 in Barcelona, Spain.

According to the findings, adding poly (ADP ribose) polymerase (PARP) inhibitor olaparib to bevacizumab extended progression-free survival (PFS) in women with advanced stage ovarian cancer, with or without a BRCA mutation.

Currently, the standard of care for most patients with newly diagnosed advanced disease is surgery and platinum-based chemotherapy combined with bevacizumab and then followed by bevacizumab alone.

“After decades of studying different chemotherapy approaches, it is the first time we have meaningfully prolonged progression free survival and hopefully we will improve long-term outcomes,” said Ana Oaknin, MD, principal investigator, Vall d’Hebron Institute of Oncology, in a statement.

Results came from the PAOLA-1/ENGOT-ov25 trial, which is the first phase 3 trial to explore the safety and efficacy of combining and PARP inhibitor with bevacizumab as first-line maintenance therapy in patients with ovarian cancer with and without the BRCA mutation.

The trial consisted of just over 800 patients who had either partial or complete response to standard platinum-based chemotherapy and bevacizumab. While some patients in the study continued on to receive bevacizumab and placebo, others received the combination of bevacizumab and olaparib. Patients received olaparib for up to 24 months and bevacizumab for 15 months.

Over a median follow-up of 24 months in the olaparib arm and 22.7 months in the placebo arm, the combination regimen produced a median PFS of 22.1 months compared with a median PFS of 16.6 months among those taking bevacizumab and placebo.

“This study reports the greatest hazard ratio (0.59) and longest progress free survival we have ever seen,” Isabelle Ray-Coquard, MD, PhD, Centre Leon Berard, Universite Claude Bernard, Lyon, and president of the GINECO group France, said in a statement. She added that compared with other trials that started randomization with the first cycle of chemotherapy, the current study started a median 6 weeks after the last cycle.

The PFS benefit associated with adding the PARP inhibitor to bevacizumab was even more significant in patients who exhibited a BRCA mutation, as well as in those with homologous recombination deficiency. Among these patients, PFS extended beyond 3 years (37.2 months).

Notably, adding olaparib to the treatment regimen did not increase side effects compared with placebo.

Oaknin argued that the results of the study should become a new standard of care for patients with advanced disease and that the trial is a significant step forward in treatment for the patient population.

 
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