The FDA has approved niraparib (Zejula®, Tesaro, Inc.) for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who experience disease progression following three or more lines of chemotherapy. Niraparib is indicated for patients whose tumors are positive for homologous recombination deficiency (HRD).
The approval was based on QUADRA (NCT02354586), a multicenter, open-label, single-arm, phase 2 trial that enrolled 463 patients with relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer, including 98 patients with HRD-positive tumors, whose disease progressed after three or more lines of chemotherapy. Patients received 300 mg of niraparib orally once daily until disease progression or unacceptable toxicity. The study's primary end points were objective response rate and duration of response, determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Niraparib achieved an overall response rate of 24% in patients whose tumors were HRD-positive, with an estimated median duration of response of 8.3 months.
Adverse reactions leading to dose reduction or interruption were experienced by 73% of patients. The most common adverse reactions included thrombocytopenia (40%), anemia (21%), nausea (13%), vomiting (11%), neutropenia (11%), fatigue (9%), and abdominal pain (5%).
"We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease," conclude the study authors, led by Kathleen N. Moore, MD, Associate Professor of Gynecologic Oncology at the University of Oklahoma Stephenson Cancer Center, in the study now published in The Lancet Oncology.
In addition, the FDA has approved the Myriad myChoice CDx test as a companion diagnostic for determining HRD tumor status. The recommended dosage of niraparib as later-line treatment for patients with HRD-positive advanced ovarian, fallopian tube, or primary peritoneal cancer is 300 mg taken orally once daily with or without food.
For More Information
Moore KN, Secord AA, Geller MA, et al (2019). Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicenter, open-label, single-arm, phase 2 trial. Lancet Oncol, 20(5):636-648. DOI:10.1016/S1470-2045(19)30029-4
Image credit: Ed Uthman. Licensed under CC BY 2.0