Clincial Trials Show Niraparib Improves PFS With Tolerable Safety Profile Following Response to Platinum-based Chemotherapy in Ovarian Cancer

Niraparib (Zejula; Zai Lab Limited) showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with a tolerable safety profile following a response to platinum-based chemotherapy regardless of biomarker status, according to the results of the phase 3 PRIME study presented at the Society of Gynecologic Oncology (SGO) annual meeting.¹ The trial assessed niraparib as maintenance therapy in patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, which were collectively termed ovarian cancer for the purposes of the study.

During the PRIME study, investigators observed that the median PFS was significantly longer for patients who were treated with niraparib compared to placebo. Specifically, they found that PFS for the niraparib group was 24.8 months compared to placebo at 8.3 months, with a hazard ratio (HR), 0.45; p<0.001.¹

“The PRIME data continue to support niraparib monotherapy as the standard of care after first-line platinum-based chemotherapy regardless of biomarker status,” said Alan Sandler, MD, president and head of global development, oncology at Zai Lab, in a press release. “More specifically, [niraparib] is the first and only PARP inhibitor approved globally, including in China, as monotherapy for all-comer patients in the first-line maintenance treatment settings.”¹

Further investigation showed that patients with germline BRCA mutations (gBRCAmut) did not reach median PFS (mPFS) versus placebo mPFS of 10.8 months, with HR and 95% CI: 0.40 (0.23, 0.68). For patients with non-gBRCAmut, the mPFS was 19.3 months compared to 8.3 months, with HR and 95% CI: 0.48 (0.34, 0.67).¹

“I believe the data of the PRIME study will have a significant impact on the clinical practice in the first-line treatment of ovarian cancer in China and beyond, as the individualized starting dose regimen has demonstrated an improved efficacy and safety profile,” said Lingying Wu, MD, director of the department of gynecologic oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, in the press release.

For data on overall survival (OS), although the results remain immature, the PRIME trial showed that the percentage of death in niraparib and placebo groups were at 14.5% versus 21.7%, respectively, demonstrating a trend in favor of niraparib at the data cut-off.¹

During a presentation by Heidi Godoy, DO, at the SGO annual meeting on the PRIMA study previously conducted by Zai Lab Limited’s partner GlaxoSmithKline, Godoy explained niraparib showed a PFS benefit for patients with advanced ovarian cancer after a response to first-line platinum-based chemotherapy compared with placebo, regardless of biomarker status.²

Additionally, the PRIMA trial assessed stage 3 and 4 epithelial cancer as they are the most common stages that patients present with, Godoy explained. The PRIMA trial looked at complete or partial response to first-line platinum-based chemotherapy, and during the trial, patients were randomized in a 2 to 1 setting to niraparib or placebo.

The primary endpoint of the PRIMA trial was mPFS in patients who had tumors with homologous recombination deficiency and mPFS in the overall population. Of the 733 patients included in the PRIMA trial assessing mPFS in the overall population, 85% had residual disease, 35% had stage 4 disease, and 67% had received neoadjuvant chemotherapy. Godoy explained that this data specifically highlights that the PRIMA trial population included patients at high risk of progression.

“In those patients who had gotten placebo it’s 8.2 month mPFS, and when you look at the treatment group it’s 13.8 months. So, this is all-comers, the entire population—you see a 38% reduction in progression of disease,” Godoy said.

Specifically, Godoy noted that the PRIMA trial investigated PFS and not OS, as trials assessing OS are far more complex and expensive.²

“Those studies cost millions and millions of dollars to do,” Godoy said. “OS is really hard to show a difference because with OS, you have to take into account the sequencing of your drugs and how people prescribe, so there are a lot more factors that go into OS as opposed to just PFS.”²

During the PRIME study, the investigators observed that the safety profile of niraparib improved with the individualized starting dosing (ISD) prospectively applied to all patients. While being treated at the prospective ISD for niraparib, fewer than 7% of patients experienced adverse events (AEs) that led them to discontinue treatment, the lowest rate of any PARP inhibitor while under investigation in a phase 3 first-line maintenance ovarian cancer trial.¹

The investigators found that the ISD reduced the incidence of hematological treatment-emergent AEs (TEAEs) compared with a previous fixed starting dose. Grade ≥3 hematological TEAEs of neutrophil count decrease in patients treated with niraparib were 17.3% versus placebo at 1.6%, while anemia and platelet count decrease were 18.0% vs. 1.6% and 14.1% vs. 0.8%, respectively.¹

REFERENCE

1. Zai Lab Presents Positive Results from Phase 3 PRIME Study of ZEJULA® (Niraparib) at Society of Gynecologic Oncology Meeting. Shanghai, China: Zai Lab Limited; March 20, 2022. [Email]
2. Godoy H. ISS VI: The only once-daily, oral PARP inhibitor monotherapy approved for all first-line platinum responders with advanced ovarian cancer, regardless of biomarker status. Society of Gynecologic Oncology 2022; March 19, 2022; Phoenix, AZ.