The FDA has granted a priority review designation to a supplemental biologics license application for niraparib (Zejula) for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 or more prior chemotherapy regimens, and who have either a BRCA mutation or have homologous recombination deficiency (HRD) and progressed >6 months after their last platinum-based chemotherapy.
The FDA has granted a priority review designation to a supplemental biologics license application for niraparib (Zejula) for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 or more prior chemotherapy regimens, and who have either a BRCA mutation or have homologous recombination deficiency (HRD) and progressed >6 months after their last platinum-based chemotherapy.1
The designation is based on findings from the QUADRA study, in which the overall response rate (ORR) was 28% (95% CI, 15.6-42.6; P = .00053) in the primary efficacy population of patients who had HRD and who received at least 3 prior lines of therapy.2Under the Prescription Drug User Fee Act, the FDA must make a decision on the application by October 24, 2019, according to a press release from GlaxoSmithKline, which has acquired Tesaro, the developer of niraparib.
“The results of the QUADRA study demonstrate that Zejula is active as a late-line treatment for patients beyond those with BRCA mutations,” Mary Lynne Hedley, PhD, president and chief operating officer of Tesaro, stated in the press release. “With this study, we continue to advance our mission to provide more patients with ovarian cancer an opportunity to benefit from treatment with Zejula.”
In the multicenter, open-label, single-arm, QUADRA study, researchers evaluated the safety and efficacy of niraparib in 463 adult patients with metastatic, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who previously received ≥3 lines of chemotherapy.
Patients received oral niraparib at 300 mg daily continuously, beginning on day 1 in 28-day cycles until disease progression. The primary endpoint was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with HRD-positive tumors—which include both patients with and without BRCA mutations—who were sensitive to their most recent platinum-based therapy who had received 3 or 4 prior anticancer therapies. Also, efficacy analyses were conducted in all dosed patients with measurable disease at baseline.
At the time of data cut-off on April 11, 2018, 21 patients remained on therapy. Patients had received a median 4 (IQR 3-5) prior lines of therapy; moreover, the median follow-up for overall survival (OS) was 12.2 months (IQR 3.7-22.1). Thirty-three percent of patients were resistant and 35% were refractory to the last administered platinum therapy.
Regarding safety, the most common treatment-related grade ≥3 treatment-emergent adverse events (AEs) were anemia (24%) and thrombocytopenia (21%). The most common treatment-emergent serious AEs were small intestinal obstruction (7%), thrombocytopenia (7%), and vomiting (6%). There was 1 death due to gastric hemorrhage that was considered to be treatment related.
Results of a posthoc analysis from the BRCA-mutant cohort (n = 63)—patients of which were also PARP inhibitor—naïve—of QUADRA were presented at the 2018 ESMO Congress, in which the ORR was 29% in this subgroup.3 The response rates were similar between those with germline and somatic BRCAmutations (25% vs 33%).
Here, the median PFS was 6.3 months, which improved to a median of 11.0 months in those who had platinum-sensitive disease. In patients with BRCA-mutant, platinum-resistant and -refractory disease had a median PFS of 5.4 months and 5.7 months, respectively.
The median OS was 26.0 months in the overall group of patients with BRCA mutations. Moreover, when examined by platinum sensitivity status, the median OS was not estimable in patients with platinum-sensitive disease and was 26.0 months and 23.3 months in those with platinum-resistant and -refractory disease, respectively.
Additionally, patients who were sensitive to the last line of platinum therapy had a clinical benefit rate (CBR) of 72% and 56% at 16 weeks and 24 weeks, respectively. The CBRs in patients with platinum-resistant disease were 38% at 16 weeks and 33% at 24 weeks, and in those with platinum-refractory disease, the CBRs were 50% and 31% at 16 and 24 weeks, respectively.
The ORR was 32% in those with BRCA1 mutations (n = 20) and 33% in those with BRCA2 mutations (n = 18).
“We know Zejula plays an important role in helping women with ovarian cancer whose disease has progressed despite initial therapy,” Hal Barron, MD, FACC, chief scientific officer and president, R&D, GlaxoSmithKline, stated in the press release. “Our hope is that over time, our ongoing clinical trials will demonstrate that this medicine can benefit even more patients.”
Niraparib was approved by the FDA in March 2017 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.
1. U.S. Food and Drug Administration accepts GSK’s application for ZEJULA (niraparib) in late stage ovarian cancer with priority review. GlaxoSmithKline. Published June 24, 2019. https://bit.ly/2Le2Alq. Accessed June 24, 2019.
2. Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4.
3. Moore KN, Secord AA, Geller MA, et al. QUADRA: a phase 2, open-label single-arm study to evaluate niraparib in patients with relapsed ovarian cancer in 4th or later line of therapy: results from the BRCAmut subset. Ann Oncol. 2018;29(8): viii332-viii358. doi: 10.1093/annonc/mdy285.
This article originally appeared on OncLive as, "FDA Grants Priority Review to Niraparib for Late-Stage Ovarian Cancer."