Ed. note: Niraparib (Zejula) was approved by the U.S. Food and Drug Administration (FDA) on March 28, 2017, as a maintenance therapy for women with ovarian, fallopian tube, or primary peritoneal cancer. This post was originally published on Oct. 21, 2016.
For women with relapsed ovarian cancer that responds to platinum-based chemotherapy, a drug that hampers cancer cells from repairing damaged DNA can significantly lengthen the period in which the disease is held in remission, according to a new study by Dana-Farber researchers and international collaborators.
In a phase three clinical trial involving 553 patients with platinum-sensitive ovarian cancer, the drug niraparib substantially lengthened progression-free survival (PFS) – how long a patient lives before their disease begins to worsen – compared to a placebo. The improvement occurred across all subgroups of participants, demonstrating niraparib’s broad effectiveness for patients with relapsed platinum-sensitive ovarian cancer, study leaders say.
The findings of the trial, dubbed ENGOT-OV16/NOVA, were simultaneously published in the New England Journal of Medicine and presented at the European Society for Medical Oncology 2016 Congress in Copenhagen.
Known as a PARP inhibitor, niraparib works by hindering DNA repair in cancer cells that are particularly vulnerable because of malfunctions in DNA-repair pathways. In clinical trials, PARP inhibitors have shown promise against cancers that carry mutations in the DNA-repair genes BRCA1 or BRCA2.
“The results of this trial are particularly encouraging because niraparib showed effectiveness not only in cancers that harbored BRCA mutations or showed other signs of being deficient in DNA repair, but in all participants enrolled in the study,” said the study’s senior author, Ursula Matulonis, MD, interim director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber and medical director of Gynecologic Oncology at the Susan F. Smith Center. “This indicates the use of PARP inhibitors can be extended beyond BRCA-related cancers.”
The participants had ovarian cancer that initially responded to platinum-based chemotherapy and later recurred, but remained sensitive to platinum drugs – a category that accounts for about 50 percent of all ovarian cancer patients with recurrent cancer. Upon enrolling, they were randomly assigned to receive 300 milligrams of niraparib – or a placebo – once daily.
The benefit of niraparib was widespread. Among participants whose tumors carried a BRCA mutation, progression-free survival was 21 months for those who received niraparib versus 5.5 months for those who received a placebo. For patients whose tumors lacked BRCA mutations but still had DNA-repair problems, PFS was 12.9 months for the niraparib group vs. 3.8 months for the placebo group. Overall, patients whose tumors were negative for BRCA mutations had a PFS of 9.3 months if they received niraparib and 3.9 months if they received a placebo.
The side effects of niraparib therapy were tolerable for the vast majority of patients, investigators found. In cases where the side effects were severe, they could be managed by reducing the dose.
“Our findings show a positive effect for niraparib in patients with relapsed platinum-sensitive ovarian cancer,” Matulonis remarks. “The results are consistent for all participants in the NOVA study, suggesting that all patients with high-grade relapsed platinum-sensitive ovarian cancer who respond to further platinum should be considered for niraparib treatment.”