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FDA Approves Niraparib for Ovarian Cancer

Jason M. Broderick @jasoncology
Published: Monday, Mar 27, 2017

The FDA has approved the PARP inhibitor niraparib (Zejula) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

 <.001). The median time to subsequent therapy was 21 months with niraparib versus 8.4 months with placebo (HR, 0.31; 95% CI, 0.21-0.48).

The median time to progression or death during the first subsequent therapy following the study (PFS2) was 25.8 months for those who received maintenance niraparib versus 19.5 months for placebo (HR, 0.48; 95% CI, 0.28-0.82; P = .006).

Findings for overall survival were not yet mature (fewer than 20% of events). At the time of the analysis, niraparib had reduced the risk of death by 27% versus placebo, although this finding was not statistically significant (HR, 0.73; 95% CI, 0.480-1.125; P = .1545).

In patients with HRD-positive, BRCA wild-type tumors, median PFS was 9.3 versus 3.7 months for niraparib and placebo, respectively (HR, 0.38; 95% CI, 0.23-0.63; P <.001). In those with HRD-positive, somatic BRCA-mutated tumors, the median PFS was 20.9 months with niraparib versus 11.0 months for placebo (HR, 0.27; 95% CI, 0.08-0.90; P = .02). In patients with HRD-negative, non-germline BRCA-mutated tumors, median PFS was 6.9 versus 3.8 months for niraparib and placebo, respectively (HR, 0.58; 95% CI, 0.36-0.92; P = .02).

In those with non-germline BRCA mutations regardless of HRD status, the median chemotherapy-free interval was 12.7 versus 8.6 months for niraparib and placebo, respectively (HR, 0.50; 95% CI, 0.37-0.67; P <.001). The median time to subsequent therapy was 11.8 versus 7.2 months (HR, 0.55; 95% CI, 0.41-0.72; P <.001) and the median PFS2 was 18.6 and 15.6 months for the niraparib and placebo arms, respectively (HR, 0.69; 95% CI, 0.49-0.96; P = .03).

Across cohorts, 14.7% of 367 niraparib-treated patients discontinued therapy due to an adverse event (AE) compared with 2.2% of the 179 patients in the placebo arm. There were no treatment-related deaths in the study. In the follow-up period, 1 patient in the niraparib arm and 2 in the placebo group died of myelodysplastic syndrome or acute myeloid leukemia. One of these deaths in each arm was deemed to be treatment related.

“The approval of Zejula, the first maintenance therapy approved in the United States for recurrent ovarian cancer, is extremely encouraging for the ovarian cancer community,” Mansoor Raza Mirza, MD, ENGOT-OV16/NOVA study chair and medical director of the Nordic Society of Gynaecological Oncology (NSGO), said in a statement. “The unique design of the NOVA study, which included women both with and without germline BRCA mutations, allowed us to determine that Zejula provides significant progression-free survival improvement in a very broad patient population. Having the option of prescribing Zejula without the need for a diagnostic test could fundamentally change the way we treat this disease from ‘watch and wait’ after a response to chemotherapy, to active treatment. With the significant increase in PFS observed in NOVA, I believe that we are changing the course of disease for patients with ovarian cancer, regardless of platinum sensitivity and independent of BRCA mutation or biomarker status.” 

The most common all-grade AEs for niraparib versus placebo, respectively, were nausea (73.6% vs 35.2%, respectively), thrombocytopenia (61.3% vs 5.6%), fatigue (59.4% vs 41.3%), anemia (50.1% vs 6.7%), constipation (39.8% vs 20.1%), vomiting (34.3% vs 16.2%), and neutropenia (30.2% vs 6.1%).

The most common grade 3/4 AEs in the niraparib arm were hematologic, and included thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%). The most common non-hematologic AEs were hypertension (8.2%), fatigue (8.2%), and nausea (3%). A majority of hematologic AEs were experienced in the first 3 cycles.

Tesaro, the manufacturer of niraparib, initiated a rolling submission of data from the NOVA trial for a new drug application in September 2016, after receiving a fast track designation from the FDA. In its statement today, the company reported that it anticipates that niraparib will be officially launched in the United States in late April.

“We are so gratified to bring this unique new medicine to women with ovarian cancer, and would like to thank the patients who gave selflessly to participate in this trial with the assistance of their caregivers and physicians. We consider clinical trial participants to be the most important contributors to the success of the Zejula clinical development program,” Mary Lynne Hedley, PhD, president and chief operating officer of Tesaro, said in a statement. “We would also like to express our appreciation to the FDA for its rapid and thorough assessment of the Zejula application in less than 3 months after it was accepted for review, as well as our partners at ENGOT for their diligence and care in executing the NOVA clinical trial. Tesaro is committed to supporting women bravely facing ovarian cancer and we are planning to work with patients, healthcare providers and payers to ensure access to this paradigm-changing medicine.”

References

  1. Mirza MR, Monk BJ, Oza A, et al. A randomized, double-blind phase 3 trial of maintenance therapy with niraparib vs placebo in patients with platinum-sensitive recurrent ovarian cancer (ENGOT-OV16/NOVA trial). Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA3_PR.
  2. Mirza MR, Monk B, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive recurrent ovarian cancer [published online October 8, 2016]. N Engl J Med. DOI: 10.1056/NEJMoa1611310.

 



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