Ovarian cancer patients with recurrent, platinum-sensitive disease may benefit greatly from niraparib maintenance treatment, according to data from a Phase 3 trial in which niraparib significantly prolonged patients’ progression-free survival compared to placebo.
Findings of the study, “Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer,” were presented recently for the first time at the European Society for Medical Oncology (ESMO) 2016 Congress, and published in The New England Journal of Medicine.
“There are limited treatment options in recurrent ovarian cancer,” said lead author Mansoor Raza Mirza, MD, chief oncologist, Rigshospitalet, Copenhagen University Hospital, Denmark and medical director of the Nordic Society of Gynaecological Oncology (NSGO), in a press release. “Cumulative toxicity with platinum-based chemotherapy and lack of additional benefit limits its use. We then pause treatment until the next relapse and start combination chemotherapy,” he said.
“The current options for maintenance therapy in the EU are bevacizumab [marketed as Avastin], which can only be given once and improves progression-free survival by just a few months, and the PARP inhibitor olaparib [marketed as Lynparza], which is only approved in patients with a germline BRCA mutation (about 10-15% of ovarian cancer patients). No maintenance therapy is approved outside the EU,” he added.
Niraparib, a PARP inhibitor, induces cancer cell death by preventing the proper repair of damages in the DNA, and has emerged as a promising therapy for ovarian cancer patients, with low frequency of severe side effects.
To address whether niraparib was suitable as a maintenance therapy for platinum-sensitive ovarian cancer patients, the European Network for Gynecological Oncological Trial groups and investigators in the U.S., Canada and Hungary conduced the ENGOT-OV16/NOVA study (NCT01847274), a randomized, double-blind, Phase 3 trial evaluating the safety and efficacy of niraparib versus placebo in patients with recurrent ovarian cancer who responded to platinum-based therapy.
The study enrolled 553 patients who were assigned to specific cohorts based on their BRCA mutation status and randomized to receive either niraparib (300 mg once daily continuously during a 28-day cycle), or placebo. Among the enrolled participants, 203 had BRCA germline mutations.
Results revealed that the study met its primary endpoint, with niraparib significantly improving patients’ progression-free survival. This was observed irrespective of patients’ BRCA mutation status.
Indeed, inpatients in BRCA mutation, niraparib more than tripled patients’ time to disease progression, showing a median progression-free survival of 21 months compared to the 5.5 months observed in placebo-treated patients. In patients without BRCA mutations the effect wasn’t so striking, but was still clinically significant; median PFS for in the niraparib group was 9.3 months, and 3.9 months in the placebo group.
In addition, patients who had normal BRCA, but had mutations in other genes involved in DNA repair, also saw their time to disease progression increased with niraparib maintenance therapy; 12.9 months versus 3.8 months on the placebo group.
Grade 3 or grade 4 adverse events were observed in more than 10 percent of niraparib-treated patients, with the most common adverse events including reduced platelet number, anemia, and neutropenia (reduced number of a type of immune cells called neutrophils). All these, however, were resolved upon dose adjustments.
In addition, patients on the niraparib and placebo groups reported similar quality-of-life outcomes.
ENGOT-OV16/NOVA results also revealed significant improvements in all secondary endpoints, with niraparib increasing the second progression-free survival, chemotherapy-free interval, and overall survival. This was observed in all three groups; BRCA mutation, BRCA mutation-free, and non-BRCA DNA repair mutation.
“This is a breakthrough for patients with ovarian cancer,” said Mirza. “We have never seen such large benefits in progression-free survival in recurrent ovarian cancer. Niraparib significantly improved all endpoints across a broad patient population representing 70% of all ovarian cancer patients. These landmark results could change the way we treat this disease,” he said.
“Once it is approved by the regulatory authorities, I’ll consider niraparib for all my patients with recurrent ovarian cancer who respond to platinum, regardless of BRCA status,” he added.
Andrés Poveda, MD, head of the Gynaecological Cancer Clinic, Oncology Foundation Institute, Valencia, Spain applauded the inclusion of patients with non-BRCA DNA damage repair mutations, but noted that further studies are required to understand which of these patients will not respond to PARP inhibitors, and why.
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