Maintenance treatment with Zejula (niraparib) prolongs the time lived without disease worsening in women with newly diagnosed advanced ovarian cancer who are responding to their first-line platinum-based chemotherapy — regardless of mutations in DNA repair genes — a Phase 3 clinical trial has shown.
Patients treated with Zejula lived a median of 5.6 months more compared with those receiving a placebo. The therapy led to an even greater benefit – a median lengthening of 11.5 months – in women who had tumors defective in DNA repair, a status termed “homologous recombination deficiency” (HRD).
GSK, the owner of Zejula, plans to use this data to ask for an extension of the therapy’s approved indication by the end of 2019.
The trial results were presented Sept. 28 at the European Society for Medical Oncology (ESMO) 2019 congress, held in Barcelona, Spain, and simultaneously made available in a more detailed report “Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer,” published in the journal New England Journal of Medicine.
Zejula is a once-daily, oral medicine indicated for maintenance treatment of women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have had a response (complete or partial) to platinum-based chemotherapy (usually cisplatin or carboplatin).
The standard treatment for newly diagnosed advanced ovarian cancer consists of tumor reduction surgery plus platinum–taxane chemotherapy. This approach is still very ineffective, with up to 85% of the patients having the disease recur after treatment, and because the use of additional therapies is limited by safety concerns.
Building on prior results with PARP inhibitors, Tesaro went on to evaluate Zejula’s effectiveness and safety for this hard-to-treat population on the PRIMA trial (PRIMA/ENGOTOV26/GOG-3012; NCT02655016), a Phase 3, double-blind, randomized, placebo-controlled study. The trial was conducted in 20 countries at 181 clinical sites.
The trial’s primary objective was to evaluate Zejula as a maintenance therapy in women with newly diagnosed advanced cancer of the ovary, peritoneum, or fallopian tube, who have responded to first-line platinum-based chemotherapy and were at high risk for relapse, with or without BRCA mutations.
A total of 733 women were included. Within 12 weeks after completion of the last dose of chemotherapy, women were randomized to receive 300 mg of Zejula (487 patients), or placebo (246 patients), given once daily in 28-day cycles, for 36 months or until disease progression.
About half the patients (51%) had tumors positive for homologous recombination deficiency (HRD), a status frequently used to identify patients most likely to benefit from certain cancer therapies like PARP inhibitors. HRD status was measured by Myriad‘s myChoice test.
Patients in the overall population treated with Zejula lived significantly longer with no signs of disease progression (progression-free survival, PFS) compared to similar patients receiving placebo — a median of 13.8 months compared to 8.2 months in the placebo group.
This meant that patients taking Zejula were 38% less likely to experience disease progression or die.
The survival benefit was even greater among patients who had HRD positive tumors (including those who had BRCA mutations), whose median PFS was 21.9 months with Zejula versus 10.4 months with a placebo. This corresponded to a 57% reduction in the risk of disease progression or death.
In an interim analysis done at 24 months after the study began, overall survival demonstrated a trend favoring Zejula — 84% and 77% of patients were alive in the Zejula and placebo groups, respectively.
Additionally, all patient groups (including HRD positive, negative and unknown status) showed a sustained and durable treatment effect.
Regarding safety, no new signals were identified for Zejula. Myelosuppressive side effects (a reduction of bone marrow’s ability to make blood cells) and low-grade nausea were more common under the therapy than on placebo.
The most common adverse side effects graded as severe or worse were low red blood cell counts (31.0%), low platelet counts (28.7%), and low levels of neutrophils (a type of white blood cell, 12.8%). No treatment-related deaths occurred.
“The PRIMA study demonstrated the importance of maintenance therapy and the benefit that niraparib provided to women with ovarian cancer. I believe that niraparib monotherapy after surgery and platinum-based chemotherapy could be an important new treatment option for patients,” the principal investigator of PRIMA, Antonio Gonzalez, MD, said in a GSK press release. Gonzalez is co-director at the Clinica Universidad de Navarra, Spain.
“Ovarian cancer is the eighth most commonly occurring cancer in women worldwide and women with this devastating disease have a five-year survival rate of less than 50%. PRIMA is a landmark study as we believe these data have the potential to fundamentally change how women with ovarian cancer are treated,” said Hal Barron, MD, chief scientific officer and president of GSK research and development.
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