Zejula Receives FDA Approval for HRD-Positive Advanced Ovarian Cancer

December 2019, Vol 10, No 6 - FDA Approvals, News & Updates


On October 23, 2019, the FDA approved a new indication for the PARP inhibitor niraparib (Zejula; ­Tesaro) for the treatment of patients with homologous recombination deficiency repair (HRD)-positive advanced ovarian, fallopian tube, or primary peritoneal cancer, after receiving ≥3 chemotherapy regimens. HRD is defined by a deleterious or suspected deleterious BRCA mutation, or a genomic instability associated with disease progression more than 6 months after the ­tumor’s response to the last platinum-­based chemotherapy. On the same day, the FDA also approved the Myriad myChoice CDx test to select patients for niraparib therapy based on the HRD tumor status.

The approval of niraparib for this indication was based on a single-arm clinical trial of 98 patients with HRD-positive advanced ovarian cancer. The FDA granted this application priority review. All patients received ≥3 previous lines of chemotherapy. Patients who had previously received a PARP inhibitor were excluded from the study. Patients without BRCA mutations had to have disease progression at least 6 months after the last dose of platinum-based therapy. HRD-positive status was determined by the Myriad myChoice CDx test. All patients received 300 mg of niraparib once daily, until disease progression or unacceptable toxicity.

The primary efficacy end points were objective response rate (ORR) and duration of response. In the cohort of 98 patients with HRD-positive status, the ORR was 24% (95% confidence interval [CI], 16-34). All the responses were partial. The estimated median duration of response was 8.3 months (95% CI, 6.5-not estimable).

Among patients with ovarian cancer and BRCA mutations (N = 63), the ORR was 39% (95% CI, 17-64) in those with platinum-sensitive disease; 29% (95% CI, 11-52) in those with platinum-resistant disease; and 19% (95% CI, 4-46) in those with platinum-­refractory disease.

A total of 73% of patients had adverse reactions to niraparib that led to dose reduction or interruption. The most common (≥5%) side effects resulting in dose reduction or interruption were thrombocytopenia (40%), anemia (21%), neutropenia (11%), nausea (13%), vomiting (11%), fatigue (9%), and abdominal pain (5%).