04 Aug Prime Study: Promising Results of Niraparib in Newly Diagnosed Advanced Ovarian Cancer Reported in JAMA Oncology
MedicalResearch.com: What is the background for this study?
Response: Zai lab is focused on discovering and developing innovative therapies that will help address medical conditions where there are serious unmet needs. Advanced ovarian cancer, with a low survival and high recurrence rate, is a key focus of our oncology R&D research. In addition to our own discovery program, as part of our open innovation model we partner with companies to license drugs for patients in China and co-develop therapies to address leading causes of cancer death. We currently have a license and collaboration agreement with GSK for the development and commercialization of ZEJULA (niraparib) in mainland China, Hong Kong, and Macau.
PRIME was a follow-on study to a previously conducted study called PRIMA, which demonstrated clinical benefit of niraparib in newly diagnosed patients with advanced ovarian cancer regardless of biomarker status. The PRIMA study enrolled a population at high risk of recurrence. Thirty-five percent of patients in PRIMA received an individualized starting dose (ISD) of niraparib based on their baseline weight and platelet count. To further evaluate the efficacy and safety of niraparib with an ISD in a broad population, we decided to conduct the PRIME study. We wanted to explore further whether we could decrease toxicity using an ISD and how it would affect clinical outcomes.
The Phase 3 PRIME study was conducted at 29 hospitals in mainland China. PRIME was a randomized, placebo-controlled trial designed to evaluate the efficacy and safety of niraparib at an ISD as first-line maintenance therapy in a broad range of patients with newly diagnosed advanced ovarian cancer. All patients in PRIME received an ISD based on their baseline body weight and platelet count.
MedicalResearch.com: What are the main findings?
Response: Results show that niraparib with an ISD provided a clinically and statistically significant benefit vs. placebo and demonstrated a manageable safety profile. In the intention-to-treat population (ITT), niraparib reduced the risk of disease progression or death by 55% vs. placebo, and significantly extended progression-free survival with median PFS with niraparib of 24.8 months versus placebo of 8.3 months (HR 0.45, 95%CI 0.34-0.60, p<0.001), regardless of postoperative residual disease or biomarker status. Importantly, discontinuation due to treatment-emergent adverse events (TEAEs) with niraparib was similar to placebo (6.7% vs 5.4%).
MedicalResearch.com: What should readers take away from your report?
Response: The first important takeaway from the PRIME study is that ZEJULA with ISD significantly extended PFS versus placebo and reduced the risk of disease progression or death by 55% in all treated patients in the first-line maintenance. These findings further support the use of ISD in clinical practice.
The second takeaway is that niraparib monotherapy treatment effects are widely observed regardless of biomarker status or postoperative residual disease status.
Specifically, niraparib reduced the risk of disease progression or death by 60% in patients with germline BRCA mutation, with median PFS not reached at the time of data-cut off with median follow up for 27.5months, compared to 10.8 months in the placebo group. Patients with homologous recombination deficiency and proficiency also benefited from maintenance niraparib. In patients without a germline BRCA mutation, niraparib monotherapy reduced the risk of disease progression by 52% and extended median PFS to 19.3 months compared to 8.3 months in the placebo group.
Similarly, niraparib significantly extended mPFS to over two years (24.8 months) compared to 8.3 months in those with optimal debulking; for those patients with suboptimal debulking, niraparib extended PFS to 16.5 months compared to 8.3 months in the placebo group.
And third, an ISD of niraparib was safe and tolerable in the first-line maintenance setting. It led to an improved safety and tolerability profile of niraparib as compared to a fixed starting dose of 300 mg QD.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: The validated ISD with niraparib provides greater tolerability and a clinically meaningful improvement in PFS. It may facilitate the use of combination therapies in the frontline setting.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: Zai Lab is committed to bringing first-in-class and/or best-in-class therapeutics to address significant unmet medical needs. With the strong track record established by our niraparib development program, we are now collaborating with Seagen to bring a first-in-class tissue factor targeted ADC tisotumab vedotin (tivdak) to China. Currently the Phase 3 trial of tivdak versus physician’s choice of chemotherapy as 2L/3L in recurrent/metastatic cervical cancer is ongoing in China. Stay tuned!
Li N, Zhu J, Yin R, et al. Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. Published online July 13, 2023. doi:10.1001/jamaoncol.2023.2283
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