Olaparib Plus Bevacizumab Receives FDA Approval as Maintenance Treatment for Ovarian, Fallopian Tube or Primary Peritoneal Cancer

On May 8, 2020, the US Food and Drug Administration (FDA) approved olaparib (Lynparza), an oral pill targeting genetic alterations, in combination with bevacizumab as first-line maintenance treatment for patients with advanced ovarian, fallopian tube or primary peritoneal cancer.

This two-drug combination was approved for patients who:

• had a complete or partial response to platinum-based chemotherapy and
• had cancer associated with a deleterious or suspected deleterious BRCA mutation and / or genomic instability, defining a positive homologous recombination deficiency (HDR) status.

The approval was for maintenance after first-line treatment. The FDA also approved the Myriad myChoice® CDx test (Myriad Genetic Laboratories, Inc.) as a diagnostic test for HDR status for the use of olaparib.

The PAOLA-1 Study

The efficacy of this new combination treatment was investigated after first-line platinum-based chemotherapy and bevacizumab in patients with advanced high-grade epithelial ovarian, fallopian tube and peritoneal cancer, comparing olaparib plus bevacizumab with placebo plus bevacizumab in PAOLA-1, a randomized, double-blind, placebo-controlled, multicenter study.

Randomization was stratified by first-line treatment outcome and tumor BRCA mutation (tBRCAm) status determined by testing. All available clinical specimens were retrospectively tested with the Myriad myChoice® CDX test. Patients were randomized in a 2:1 ratio:

• 537 patients received olaparib tablets at 300 mg 2 times daily plus bevacizumab at 15 mg/kg every three weeks,
• 269 patients received placebo plus bevacizumab.

Patients started olaparib at least 3 weeks and no more than 9 weeks after their last chemotherapy dose. Olaparib continued for up to 2 years, until disease progression or until unacceptable adverse effects.

Results

The main efficacy outcome measure was investigator-assessed progression-free survival (PFS). Overall survival was an additional efficacy endpoint.

In the subgroup of 387 patients with HRD-positive tumors, median PFS was 37.2 months with bevacizumab plus olaparib versus 17.7 months in the placebo plus bevacizumab arm (HR 0.33; 95% CI: 0.25-0.45).

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

The recommended olaparib dose is 300 mg twice daily, taken with or without food. When used with olaparib, the recommended bevacizumab dose is 15 mg/kg intravenously every three weeks. * - The Latest Developments in Ovarian Cancer Treatment *