COPENHAGEN, Denmark — Niraparib maintenance therapy significantly extended PFS compared with placebo in women with platinum-sensitive recurrent ovarian cancer, according to phase 3 study results presented at the European Society for Medical Oncology Congress.
Researchers observed the benefit regardless of patients BRCA mutation or homologous recombination deficiency status.
“Patients with ovarian cancer who relapse typically get six courses of chemotherapy, wait until their next relapse and then get their next therapy,” Mansoor Raza Mirza, MD, chief oncologist in the department of oncology at Rigshospitalet — the Copenhagen University Hospital in Denmark, said during a press conference. “Treatment intervals get shorter and, eventually, all patients die of their disease. There is a real need to extend the time from one therapy to the next with less toxic treatments.”
Prior phase 1 and phase 2 trials suggested niraparib (Tesaro) — an oral PARP 1/2 inhibitor — has clinical activity in women with ovarian cancer.
Mirza and colleagues conducted an international, randomized, double blind, phase 3 trial to evaluate the efficacy of maintenance niraparib compared with placebo in 553 women with platinum-sensitive recurrent disease.
The majority (60%) of women had two prior lines of therapy, and 40% had undergone three or more prior therapies. About three-quarters (76%) of women had stage IIIc or stage IV disease.
Researchers randomly assigned women 2:1 to once-daily niraparib 300 mg or placebo. The investigators stratified results based on germline BRCA mutation status.
The analysis included 203 women with germline BRCA mutations (niraparib, n = 138; placebo, n = 65) and 350 without germline BRCA mutations (niraparib, n = 234; placebo, n = 116).
PFS served as the primary endpoint.
Researchers reported significantly longer median PFS among niraparib-treated patients in all three primary efficacy populations. These included germline BRCA mutations (21 months vs. 5.5 months; HR = 0.27; 95% CI, 017-0.41); non-BRCA mutation carriers who were homologous recombination deficiency positive (12.9 months vs. 3.8 months; HR = 0.38; 95% CI, 0.24-0.59); and all non-BRCA mutation carriers (9.3 months vs. 3.9 months; HR = 0.45; 95% CI, 0.34-0.61; P < .001 for all comparisons).
Niraparib-treated patients also experienced significantly longer chemotherapy-free interval and time to next subsequent treatment.
The most frequently reported grade 3 or grade 4 adverse events observed in niraparib-treated patients were thrombocytopenia (33.8%), anemia (25.3%) and neutropenia (19.6%). These events were managed with dose modifications.
Researchers observed no detrimental effects on quality of life with niraparib, and most patients remained on treatment until disease progression.
“Niraparib significantly improved PFS in patients with platinum-sensitive recurrent ovarian cancer, regardless of BRCA mutation [status],” Mirza said. “These landmark results warrant niraparib maintenance treatment to [the] whole study population.”
Pending regulatory approval of niraparib, the study could double the number of patients who could derive benefit from a PARP inhibitor, according to Andres Poveda, MD, head of the Gynaecological Cancer Clinic at Oncology Foundation Institute in Valencia, Spain.
“Personalized medicine has arrived in high-grade serous ovarian cancer,” Poveda, who was not involved with the study, said in a press release. “This was the first trial to use homologous recombination deficiency to select patients for treatment and showed that it is a useful strategy. We also know that PARP inhibitors benefit patients with BRCA mutations.
“Future studies are needed to unravel which patients with homologous recombination deficiency are not responders to PARP inhibitors and why, and which patients are long responders and why. We also need to know if there are other non-homologous recombination deficiency factors, such as cyclin E positivity, that predict which patients will respond to treatment.” – by Mark Leiser
For more information: Mirza M, et al. Abstract LBA3_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Tesaro provided funding for this study. Mirza reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.