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DNA repair-blocking drug substantially improves progression free survival for common form of recurrent ovarian cancer, international trial finds

  • Ursula Matulonis, MD

    In women with relapsed ovarian cancer that is sensitive and responsive to platinum, a drug that hampers cancer cells from repairing damaged DNA can significantly extend the period in which the disease is held in remission, researchers at Dana-Farber Cancer Institute and collaborators around the world report in a new study.

    The findings, simultaneously published on October 8, 2016 in the New England Journal of Medicine and presented at the European Society for Medical Oncology 2016 Congress in Copenhagen, apply to women with recurrent ovarian cancer that is platinum sensitive, meaning responsive to platinum-based chemotherapy regimens. In an international phase 3 clinical trial involving 553 patients with platinum sensitive ovarian cancer, the PARP inhibitor niraparib lengthened progression-free survival (PFS) – how long patients live before the disease begins to worsen – substantially compared to a placebo.

    Importantly, this improvement in PFS occurred across all subgroups of patients participating in the trial, demonstrating niraparib’s broad effectiveness for patients with relapsed platinum-sensitive ovarian cancer, study leaders say.

    Niraparib is an oral drug known as a poly (adenosine diphosphate [ADP]-ribose) polymerase – or PARP – inhibitor. It works by impeding 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 new trial, known as the ENGOT-OV16/NOVA trial, is the first successful phase 3 trial of a PARP inhibitor to be completed and published in ovarian cancer that demonstrates expanded benefit of the PARP inhibitor niraparib in all subgroups of platinum sensitive ovarian cancer, thus extending the use of PARP inhibitors beyond BRCA-related cancer.

    “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, medical director of Gynecologic Oncology at the Susan F. Smith Center for Women’s Cancers at Dana-Farber.

    The patients in the trial 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 mg of niraparib or a placebo once daily.

    The positive effect of niraparib was evident in all subsets of participants in the trial. Among those whose tumors carried a BRCA mutation, progression-free survival (PFS) was 21 months for those who received niraparib vs. 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 the 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 suggests that all patients with high-grade relapsed platinum sensitive ovarian cancer who respond to further platinum should be considered for niraparib treatment.”

    Financial support for the study was provided by Tesaro, Inc.

Posted on October 08, 2016

  • Treatments & Procedures
  • Ursula A. Matulonis, MD
  • Ovarian Cancer
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