FDA Approves myChoice CDx as Companion Diagnostic for Olaparib in Ovarian Cancer

The FDA has approved myChoice CDx for use as a companion diagnostic to identify patients with advanced ovarian cancer with positive homologous recombination deficiency (HRD) status, making them eligible to receive frontline maintenance treatment with olaparib (Lynparza) plus bevacizumab (Avastin).1

The FDA recently approved the combination of olaparib and bevacizumab for the maintenance treatment of patients with advanced ovarian cancer who are in complete or partial response (PR) to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.2 Patients’ eligibility for therapy must be established by an FDA-approved companion diagnostic for olaparib.

“We congratulate AstraZeneca and Merck on obtaining another FDA approval of Lynparza for women with advanced ovarian cancer,” Nicole Lambert, president of Myriad Oncology and Women’s Health, stated in a press release. “The approval of the myChoice CDx test will help clinicians quickly identify the potential 1 in 2 women whose ovarian cancer is HRD positive and who will likely respond to targeted therapy.

The approval of olaparib plus bevacizumab was based on results from the pivotal phase 3 PAOLA-1 trial, in which the combination reduced the risk of disease progression or death compared with bevacizumab alone. The benefit with the addition of olaparib was most pronounced in patients with HRD-positive tumors, including tumors that had BRCA mutations (HR, 0.33; 95% CI, 0.25-0.45). In this subgroup, the median progression-free survival (PFS) was 37.2 months and 17.7 months with the olaparib combination and bevacizumab alone, respectively. In those who had HRD-positive tumors without BRCA mutations, the median PFS was 28.1 months with olaparib/bevacizumab and 16.6 months with bevacizumab alone, respectively (HR, 0.43; 95% CI, 0.28-0.66).

In the ITT population, the combination led to an investigator-assessed 41% reduction in the risk of disease progression or death compared with bevacizumab alone (HR, 0.59; 95% CI, 0.49-0.72; P <.001). Additionally, after a median follow-up of 22.9 months, the median PFS was 22.1 months and 16.6 months with the combination and bevacizumab alone, respectively.

In the double-blind, placebo-controlled, phase 3 PAOLA-1 trial, patients with newly diagnosed, advanced, FIGO stage III to IV, high-grade, serous or endometria ovarian, fallopian tube, or peritoneal cancer who had a complete response (CR) or PR to frontline platinum-based chemotherapy and bevacizumab, regardless of genetic biomarker status or their outcome to prior surgery, were randomized 2:1 to receive olaparib in combination with bevacizumab (n = 537) or bevacizumab with placebo (n = 269) as a first-line maintenance treatment. Bevacizumab was administered at 15 mg/kg every 3 weeks on day 1; in the experimental arm, olaparib was given at 300 mg twice daily.

Patients were enrolled regardless of the type or extent of surgery (upfront or interval). The median age was 60.5 years, and all patients had an ECOG performance status of 0 or 1. A total of 95.5% patients had serous histology.

“The approval of the myChoice CDx test builds on our shared goal with Myriad to accelerate precision diagnosis and treatment for women with advanced ovarian cancer,” Ruth March, senior vice president, Precision Medicine, AstraZeneca, stated in the press release. “We are excited that women with advanced ovarian cancer who test positive for HRD with the myChoice CDx test at time of diagnosis can now access Lynparza in the first-line maintenance treatment setting in combination with bevacizumab.”

References

1. Myriad Receives FDA Approval of myChoice CDx® as Companion Diagnostic for Lynparza™ (olaparib) In Patients with Advanced Ovarian Cancer. Published May 11, 2020. https://bit.ly/35Pxbhj. Accessed May 11, 2020.
2. Highlights of olaparib (Lynparza) prescribing information. FDA. Updated May 8, 2020. https://bit.ly/2Wfjsgz. Accessed May 8, 2020.