FDA Approves Olaparib Plus Bevacizumab as Maintenance Treatment for Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

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On May 8, 2020, the U.S. Food and Drug Administration (FDA) expanded the indication of olaparib (Lynparza) to include its combination with bevacizumab for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status, defined by either a deleterious or suspected deleterious BRCA mutation and/or genomic instability.

The FDA also approved the Myriad myChoice CDx as a companion diagnostic for olaparib.


Efficacy of this new indication was investigated in PAOLA-1, a randomized, double-blind, placebo-controlled, multicenter trial comparing olaparib with bevacizumab vs placebo plus bevacizumab in patients with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab. 

Randomization was stratified by first-line treatment outcome and tumor BRCA mutation status, determined by prospective local testing. All available clinical samples were retrospectively tested with the Myriad myChoice CDX test.

Patients were randomly assigned 2:1 to receive 300 mg of olaparib orally twice daily in combination with bevacizumab (n = 537) at 15 mg/kg every 3 weeks or placebo plus bevacizumab (n = 269). Patients continued bevacizumab in the maintenance setting and started olaparib after a minimum of 3 weeks and up to a maximum of 9 weeks following their last chemotherapy dose.

Olaparib was continued for up to 2 years or until disease progression or unacceptable toxicity. The major efficacy outcome measure was investigator-assessed progression-free survival evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1. An additional efficacy endpoint was overall survival.

Estimated median progression-free survival in the subgroup of 387 patients with HRD-positive tumors was 37.2 months in the olaparib/bevacizumab arm and 17.7 months in the placeb/bevacizumab arm (hazard ratio = 0.33, 95% confidence interval = 0.25–0.45). Results from a blinded independent review of progression-free survival were consistent with the investigator-assessed progression-free survival analysis. Overall survival data were not mature.

The most common adverse reactions seen with olaparib/bevacizumab treatment (≥ 10% of patients) were nausea, fatigue (including asthenia), anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache.

The recommended olaparib dose is 300 mg taken orally twice daily with or without food. When used with olaparib, the recommended bevacizumab dose is 15 mg/kg intravenously every 3 weeks.