The European Commission has approved niraparib (Zejula®; GSK), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as first-line monotherapy maintenance treatment for adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following platinum-based chemotherapy.

This approval makes niraparib the only PARP inhibitor approved in the European Union for use as a monotherapy for patients with advanced ovarian cancer, regardless of their biomarker status. PARP inhibitors block the repair of broken DNA. [1]

In Europe, ovarian cancer is the sixth deadliest cancer among women and more than 65,000 women are diagnosed each year. [2][4] Despite high response rates to platinum-based chemotherapy in the first-line, approximately 85% of women with advanced ovarian cancer will see their disease return.[3] With each recurrence, the time a woman may spend without her cancer progressing gets shorter.

“This approval of niraparib means that many more women will have the option to receive this innovative medicine earlier, potentially extending the time they may spend without their devastating cancer progressing,” noted Dr Hal Barron, Chief Scientific Officer and President R&D, GSK. [4]

FDA Approval
In April 2020, the US Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for niraparib in the United States for the same indication, which is supported by data from the pivotal phase III PRIMA study (ENGOT-OV26/GOG-3012) that demonstrated a clinically meaningful progression-free survival benefit of niraparib in the first-line maintenance setting. FDA also approved a test for HRD tumors, called myChoice CDxm, which is manufactured by Myriad Genetics.

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The PRIMA study enrolled patients with newly diagnosed advanced ovarian cancer who responded to first-line treatment with platinum-based chemotherapy, a population with high unmet needs and limited treatment options.

“Until now, only women with BRCA-mutant (BRCAm) ovarian cancer, representing just 20% of patients with advanced ovarian cancer, were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting,” explained Dr Antonio Gonzalez-Martin, Co-Director, Department of Medical Oncology, Clinica Universidad de Navarra, Spain, and Primary Investigator for PRIMA. [1][5]

“Expanding the potential use of niraparib, regardless of biomarker status, is an important step forward in treating this challenging cancer,” he added.

PRIMA study
The primary endpoint in the PRIMA study was progression free survival analysed sequentially, first in the homologous recombination deficient (HRd) population, then in the overall population. The PRIMA study significantly improved PFS for patients treated with niraparib, regardless of biomarker status. the result of the study were first published in September 28, 2019 edition of the New England Journal of Medicine.[1]

In the HRd population, niraparib resulted in a 57% reduction in the risk of disease progression or death vs. placebo (HR 0.43; 95% CI, 0.31 to 0.59; p<0.0001) and a 38% reduction in the risk of disease progression or death vs. placebo in the overall population (HR 0.62; 95% CI, 0.50 to 0.76; p<0.001). In addition, there was a 60% reduction in risk of progression in those with BRCA mutation tumours (HR 0.40; 95% CI, 0.27 to 0.62; p<0.001).

Niraparib’s safety profile, as demonstrated by the PRIMA results, was consistent with the previously observed clinical safety profile. At initiation of the PRIMA study, patients received a fixed starting dose of 300 mg of niraparib once-daily. The study was later amended to incorporate an individualised starting dose of either 200 mg or 300 mg of niraparib once-daily based on the patient’s baseline weight and/or platelet count. Lower rates of grade 3 and 4 hematologic treatment-emergent adverse events were observed with an individualised starting dose, compared to the overall population, including thrombocytopenia (21% compared to 39%), anaemia (23% compared to 31%) and neutropenia (15% compared to 21%).

Based on these results, the niraparib EU prescribing information has been updated to include the individualised starting dose once-daily based on the patient’s baseline weight and/or platelet count.

“Having a new first-line maintenance option for patients with platinum-responsive advanced ovarian cancer in Europe — regardless of BRCA mutation status — speaks to the important role of PARP inhibitors in the fight against ovarian cancer,” said Clara MacKay, Chief Executive Officer, World Ovarian Cancer Coalition.

“We are especially delighted that today’s approval means that more women in Europe who are diagnosed with ovarian cancer will have this new treatment option. We appreciate the commitment and scientific leadership required to develop innovative new therapies that address unmet needs in women’s cancer,” she concluded.

Clinical trials
A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy – NCT02655016

Highlights of prescribing information
Niraparib (Zejula®; GSK) [Prescribing Information]

[1] González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O’Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28. PMID: 31562799.
[2] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-E386. doi:10.1002/ijc.29210.
[3] Lorusso D, Mancini M, Di Rocco R, Fontanelli R, Raspagliesi F. The role of secondary surgery in recurrent ovarian cancer [published online August 5, 2012]. Int J Surg Oncol. 2012. doiL10.1155/2012/613980.
[4] The World Ovarian Cancer Coalition Atlas: Global Trends in Incidence, Mortality and Survival. World Ovarian Cancer Coalition; 2018. Accessed October 19, 2020.
[5] Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015;5(11):1137-54.

Featured image: GSK in Madrid, Spain. Photo Courtesy: © 2016 – 2020 GSK/Original photograph. Used with permission.

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