FDA Grants Priority Review to Olaparib/Bevacizumab as Maintenance Therapy for Ovarian Cancer
Posted: Monday, January 20, 2020
On January 13, AstraZeneca and Merck & Co., Inc., announced that a supplemental new drug application for the PARP inhibitor olaparib (Lynparza) in combination with bevacizumab (Avastin) has been accepted and granted Priority Review by the U.S. Food and Drug Administration as maintenance therapy for patients with advanced ovarian cancer who are in complete or partial response to first-line platinum-based chemotherapy with bevacizumab. This submission is based on results from the phase III PAOLA-1 trial, which were published in December 2019 in the The New England Journal of Medicine.
The PAOLA-1 trial compared olaparib when added to standard-of-care bevacizumab with bevacizumab alone in patients with advanced ovarian cancer in the first-line maintenance setting, regardless of their genetic biomarker status or outcome from previous surgery.
The investigator-assessed results showed that the combination therapy reduced the risk of disease progression or death by 41% based on a hazard ratio of 0.59 (95% confidence interval [CI] = 0.49–0.72; P < .001) and improved progression-free survival to a median of 22.1 months vs. 16.6 months with bevacizumab alone. The safety and tolerability profiles of olaparib and bevacizumab were consistent with previous trials for each agent.
The most common adverse events of at least 20% for olaparib plus bevacizumab compared with bevacizumab alone were fatigue (53% vs. 32%), nausea (53% vs. 22%), hypertension (46% vs. 60%), anemia (41% vs. 10%), lymphopenia (24% vs. 9%), vomiting (22% vs. 11%), and arthralgia (22% vs. 24%). The rates of overall grade 3 or higher adverse events were 57% with the combination therapy and 51% with bevacizumab alone. Adverse events led to dose interruption in 54% of patients treated with the combination therapy versus 24% with bevacizumab alone; 41% of patients who received the combination therapy had a dose reduction compared with 7% who received bevacizumab alone.