Diagnostic Assay Submitted for FDA Approval in Ovarian Cancer Indication

Myriad Genetics, Inc, has submitted a supplementary premarket approval (sPMA) application to the FDA for the myChoice CDx test for use in predicting outcomes for women with frontline platinum-responsive advanced ovarian cancer who are treated with niraparib (Zejula), a PARP inhibitor, according to a press release from Myriad Genetics, Inc., the manufacturer of the test.¹

The myChoice CDx, which is made up of tumor sequencing of theBRCA1and BRCA2genes as well as 3 proprietary technologies, is the most comprehensive assay for homologous recombination deficiency (HRD). Increased susceptibility to DNA-damaging drugs like PARP inhibitors and platinum-containing therapies results from the inability to repair double-stranded DNA breaks, which is associated with HRD.

Submission of the sPMA is based on positive data from the phase III PRIMA trial, in which patients with newly diagnosed, advanced ovarian cancer who had positive HRD status by MyChoice and a response to platinum-based chemotherapy showed survival benefit with niraparib compared with placebo.Data from the PRIMA trial were recently presentedat the 2019 European Society for Medical Oncology (ESMO) Congress and simultaneously published in the New England Journal of Medicine,which demonstrated improvement in survival for patients with HRD-positive disease.²

PRIMA randomized 733 patients 2:1 to receive either niraparib (n = 487) or placebo (n = 246) once daily within 12 weeks of completing the last cycle of chemotherapy. Patients received a fixed dose of the PARP inhibitor at 300 mg in the niraparib arm, which included an adjusted dose of 200 mg for patients who weighed less than 77 kg, a platelet count below 150K/μL, or both.

Median progression-free survival (PFS) was improved by 5.6 months with niraparib. The median PFS in the niraparib arm was 13.8 months versus 8.2 months in the placebo arm, which led to a reduction in the risk of death or progression by 38% (HR, 0.62; 95% CI, 0.50-0.76;P<.001). The median PFS was longer in patients who tested positive for HRD, at 21.9 months versus 10.4 months with niraparib and placebo, respectively (HR, 0.43; 95% CI, 0.50-0.76;&nbsp;P<.001).

The median overall survival (OS) had not been reached at the time of data cutoff, but the 24-month OS rate was 84% versus 77% in the overall population with niraparib versus placebo, respectively (HR, 0.70; 95% CI, 0.44-1.11). In the HRD-positive cohort, the 24-month OS rate with niraparib was 91% versus 85% with placebo (HR, 0.61; 95% CI, 0.27-1.39).

High rates of treatment-related adverse events (TRAEs) were experienced in both the niraparib arm (96.3%) and placebo arm (68.9%), with grade &ge;3 TRAEs reported in 65.3% versus 6.6%, respectively. The most common AEs of grade &ge;3 included anemia, in 31.0% of patients in the niraparib arm versus 1.6% with placebo; thrombocytopenia in 28.7% versus 0.4%; platelet count decrease in 13.0% versus 0%; and neutropenia in 12.8% versus 1.2%. A dose reduction was required in 70.9% of patients in the niraparib arm compared with 8.2% in the placebo arm due to AEs.

In October 2019, the PARP inhibitor wasapproved by the FDA for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancerwho are HRD positive and have been treated with at least 3 prior chemotherapy regimens.&nbsp;Niraparib was also approved by the FDA in March 2017 for the maintenance treatmentof patients with ovarian cancer in the recurrent setting.

According to the American Cancer Society, around 22,000 women are diagnosed with ovarian cancer annually in the United States and are typically diagnosed at later stages when the disease has metastasized to other areas. Roughly 20% of cases of ovarian cancer are diagnosed at early stages of the disease. It is also the cause of approximately 14,000 deaths each year. Patients with genetic mutations such asBRCA1and&nbsp;BRCA2 or those who are obese, have endometriosis, or a family history of ovarian cancer are at higher risk of ovarian cancer.

&ldquo;The myChoice CDx test provides valuable molecular insights into tumors and helps identify women with ovarian cancer who are most likely to benefit from PARP inhibitors,&rdquo; said Nicole Lambert, president of Myriad Oncology. &ldquo;This regulatory submission represents another important step forward for precision medicine and ensuring that women have access to the most advanced therapies.&rdquo;

References:

1. Myriad submits sPMA for myChoice CDx with Zejula in first-line platinum responsive advanced ovarian cancer [news release]. Salt Lake City, UT: Myriad Genetics, Inc; January 22, 2020. https://bit.ly/3aBUnld. Accessed January 23, 2020.
2. Gonzalez-Martin A, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. &nbsp;[published online September 28, 2019].&nbsp;N Engl J Med. doi: 10.1056/NEJMoa191096