Ovarian Cancer: COPENHAGEN — Patients with platinum-sensitive recurrent ovarian cancer showed significantly improved disease-free survival with niraparib (Tesaro), regardless of underlying mutation status, in the first phase 3 trial to be conducted with a poly(ADP)-ribose polymerase (PARP) inhibitor.The results showed that progression-free survival (PFS) improved by 73% in patients with a BRCA mutation and by 55% in those without such mutations.
These results follow those for olaparib (Lynparza, AstraZeneca), another PARP inhibitor, which as reported by Medscape Medical News, is approved in Europe as maintenance treatment for adults with relapsed platinum-sensitive ovarian cancer. However, labeling retricts the use of olaparib to patients with BRCA-mutated ovarian cancer, limiting its use to approximately 15% to 20% of the patient population.”We have never seen such large benefits in PFS 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 added.Andrés Poveda, MD, head of the gynecological cancer clinic, Oncology Foundation Institute, Valencia, Spain,
Study Details:In the first phase 3 trial of a PARP inhibitor as maintenance therapy in patients with recurrent ovarian cancer after at least two platinum-based regimens, researchers recruited 553 patients and determined whether they had a germline BRCA mutation.The team then randomized patients within each cohort in a 2:1 ratio to niraparib 300 mg or placebo once daily, with treatment given until disease progression, unacceptable toxicity, death, withdrawal of consent, or loss to follow-up, whichever came first. Treatment could also be stopped for up to 28 days because of hematologic toxicity, after which it could be restarted at a lower dose
Within the non-gBRCAmut group, researchers also used the novel myCHOICE homologous recombination deficiency (HRD) test (Myriad Genetics) to determine which patients had homologous recombination DNA repair deficiencies and analyzed the impact of niraparib vs placebo in the subgroup.Niraparib was again associated with a significant improvement in PFS compared with placebo in the HRD patient subgroup, with a median PFS of 12.9 vs 3.8 months (HR, 0.38; P < .0001), respectively.The most common grade 3/4 adverse events were thrombocytopenia, anemia,
“Significant Step Forward”
Study discussant Sandro Pignata, MD, PhD, director, Instituto Nazionale Tumori, IRCCS Fondazione Pascale, Napoli, Italy, described the findings as a “significant step forward in the treatment of ovarian cancer.”He said that the “main novelty” of the study compared to previous investigations with PARP inhibitors was that nongermline-mutation patients were included alongside HRD-positive individuals.
For Dr Pignata, niraparib achieved “extraordinary results” in patients with BRCA mutations “that modified the clinical history of these patients,” while the patient subgroups experienced significant benefits. He said that, overall, he feels these results will change the treatment of ovarian cancer.