FDA Approves Olaparib–Bevacizumab Combo as Maintenance for Ovarian Cancer

On May 8, 2020, the FDA expanded its approval of olaparib (Lynparza; AstraZeneca Pharmaceuticals) to include its use in combination with bevacizumab for the first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers that completely or partially responded to first-line platinum-based chemotherapy and tied to homologous recombination deficiency positive status defined by a deleterious or suspected deleterious BRCA mutation, and/or genomic instability (American Association for Cancer Research, e-mail communication, May 2020). 

On this date the FDA also approved a companion diagnostic for olaparib, the Myriad myChoice CDx (Myriad Genetic Laboratories).

This approval was based on efficacy data from the double-blind, placebo-controlled, multi-center PAOLA-1 clinical trial comparing olaparib plus bevacizumab with placebo plus bevacizumab in patients with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer who received first-line platinum-based chemotherapy and bevacizumab.

Patients were randomized based on first-line treatment outcome and tumor BRCA mutation status in a 2:1 ratio to receive olaparib 300 mg twice daily plus bevacizumab 15 mg/kg every 3 weeks (n = 537) or placebo plus bevacizumab (n = 269).

Bevacizumab was used in the maintenance setting and olaparib was initiated after a minimum of 3 weeks and maximum of 9 weeks following the last chemotherapy dose for up to 2 years or until disease progression or unacceptable toxicity occurred.

The major efficacy end point was investigator-assessed progression-free survival (PFS).

Among 387 patients with HRD-positive tumors, the estimated median was 37.2 months in the olaparib plus bevacizumab arm versus 17.7 months in the placebo plus bevacizumab arm (hazard ratio, 0.33; 95% CI, 0.25-0.45).

The most common (≥10%) adverse events associated with the use of olaparib plus bevacizumab were nausea, fatigue, anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache.—Hina Porcelli