Results from the randomized NOVA trial convinced the FDA to approve niraparib (Zejula) as maintenance treatment for adult patients with recurrent epithelial ovarian, fallopian tube, or peritoneal cancer who are sensitive to platinum-based chemotherapy.
Results from the randomized NOVA trial convinced the FDA to approve niraparib (Zejula by Tesaro, Inc) as maintenance treatment for adult patients with recurrent epithelial ovarian, fallopian tube, or peritoneal cancer who have a complete or partial response (CR or PR) to platinum-based chemotherapy. This makes niraparib the third poly ADP-ribose polymerase (PARP) inhibitor to be approved since December 2014.
The 553 patients enrolled in NOVA had been diagnosed with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received at least 2 prior treatments of platinum-based chemotherapy. About 66% of patients did not have germline BRCA mutations. Both radiographic and clinical progression were monitored.
Patients were randomized (2:1) within 8 weeks of the last therapy to either niraparib (300 mg orally daily) or matched placebo. Patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm) were assigned to the germline BRCA-mutated (gBRCAmut) cohort (n = 203), and those without germline BRCA mutations were assigned to the non-gBRCAmut cohort (n = 350). The results identified significant improvement in progression-free survival (PFS) in both the gBRCAmut and non-gBRCAmut cohorts.
Safety studies, conducted in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer found that at least 10% of patients had the following adverse reactions: thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension. Patients receiving niraparib and placebo were equally susceptible to myelodysplastic syndrome (1.4%) or acute myeloid leukemia (1.1%).
“We are so gratified to bring this unique new medicine to women with ovarian cancer, and would like to thank the patients who gave selflessly to participate in this trial with the assistance of their caregivers and physicians. We consider clinical trial participants to be the most important contributors to the success of the ZEJULA clinical development program,” said Mary Lynne Hedley, PhD, president and chief operating officer of TESARO.
Ursula Matulonis, MD, director, Gynecologic Oncology at Dana-Farber Cancer Institute and professor of medicine, Harvard Medical School, who has been involved with the clinical trials, explained that the effectiveness of platinum-based drugs diminishes in the case of ovarian cancer. “Until recently, there have been few treatment advances for women with recurrent ovarian cancer and even fewer options available for women who do not harbor BRCA mutations. We are excited to have the opportunity to offer appropriate patients an oral, once-daily maintenance treatment that reduces the risk of cancer progression and extends the time between courses of chemotherapy for patients who have few treatment options,” she said.
PARP is an enzyme that actively corrects DNA damage and PARP inhibitors are used as monotherapy against tumors with defective DNA repair, such as BRCA1/2, and are also used in combination with anticancer agents designed to cause DNA damage.
Phase 3 results from NOVA were presented at the 40th annual meeting of the European Society for Medical Oncology (ESMO) in fall 2015, from the companion diagnostic perspective. The myChoice HRD test, developed by Myriad Genetics, was tested in parallel with the drug and found that 100% of patients with a germline BRCA mutation and 55% of patients without a BRCA mutation had defects within their homologous recombination DNA repair pathway.
Tesaro is also developing niraparib for front-line treatment of ovarian cancer in combination with bevacizumab or a programmed death-1 (PD-1) inhibitor. The company also plans to initiate a combination trial of niraparib with a PD-1 inhibitor in triple-negative breast cancer, as well as lung cancer.
Niraparib is expected to be available in the market by the end of April. Olaparib (Lynparza by AstraZeneca) and rucaparib (Rubraca by Clovis Oncology) are the 2 other PARP inhibitors currently available for ovarian cancer.