Niraparib Extends PFS, Time to Next Treatment in Patients With EOC, Especially BRCA-Mutated Cases

Patients with epithelial ovarian cancer (EOC) in the homologous recombination-deficient (HRd) subgroup who received first-line maintenance (1LM) niraparib monotherapy experienced longer real-world observed median progression-free survival (rwPFS) and time to next treatment (rwTTNT), particularly those with BRCA-mutated (BRCAm) tumors, according to a study published in Future Oncology.¹

The standard of care for 1L therapy for newly diagnosed advanced EOC is a combination of primary or interval cytoreductive surgery followed by platinum-based chemotherapy, with or without bevacizumab. This approach has evolved to include subsequent 1LM therapy with bevacizumab, a poly-ADP-ribose polymerase (PARP) inhibitor, or a combination of bevacizumab and a PARP inhibitor, all of which have been shown to increase PFS among this patient population.

Niraparib, a PARP inhibitor, was approved by the FDA in 2017 as a 1LM therapy for patients with platinum-sensitive, recurrent OC based on results from the phase 3 PRIMA trial (NCT02655016).² In this trial, 1LM niraparib monotherapy demonstrated prolonged PFS in those with newly diagnosed advanced EOC who responded to 1L platinum-based chemotherapy.

However, the researchers emphasized the importance of investigating real-world outcomes for patients receiving 1LM niraparib monotherapy.¹ Therefore, they estimated rwPFS and rwTTNT among US patients receiving 1LM niraparib monotherapy in routine clinical practice.

First-line maintenance (1LM) niraparib significantly extends progression-free survival (rwPFS) and time to next treatment (rwTTNT) in patients with epithelial ovarian cancer (EOC). | Image Credit: luchschenF - stock.adobe.com

The researchers used data from Flatiron Health, a US-based, nationwide, electronic health record-derived, deidentified database to identify eligible patients with EOC. The data are from about 280 cancer clinics, representing an estimated 800 care sites, primarily in the community oncology settings.

Eligible patients were diagnosed with OC on or after January 1, 2015, and they initiated 1LM treatment with niraparib monotherapy between January 1, 2017, and December 1, 2022, following 1L platinum-based chemotherapy. Patients were followed from the date of 1LM niraparib monotherapy initiation to the last clinical activity, the end of the study, or death, whichever came first.

In terms of outcomes, observed median rwPFS and rwTTNT were measured from the end of 1L platinum-based chemotherapy until the event or censor date. The event date for rwPFS was the first occurrence of documented real-world progression or death, while patients who were alive or did not progress were censored. As for rwTTNT, the event date was the first occurrence of 2L treatment initiation or death; those without evidence of either occurring were censored at the last clinical activity.

Observed median rwPFS and rwTTNT, along with associated 95% CIs, were estimated using Kaplan-Meier methodology for the overall study population and the HRd subgroup. The HRd subgroup was further stratified to assess outcomes among those with BRCA wild-type (BRCAwt) or BRCAm tumors.

Of the 11,399 patients diagnosed with OC on or after January 1, 2011, 560 were included in the overall study population, with 144 in the HRd subgroup. The median age was 67 (IQR, 61-75) in the overall population and 64 (IQR, 57-73) in the HRd subgroup.

Patients in the overall population were mostly White (n = 342; 61.1%), diagnosed with stage III (n = 282; 50.4%) or IV (n = 179; 32.0%) disease, and received care in community oncology settings (n = 473; 84.5%). Additionally, the median follow-up time for patients in the HRd subgroup (17.0 months; 95% CI, 9.3-26.1) was longer than for those in the overall population (14.2 months; 95% CI, 7.4-23.6).

The researchers determined the observed median rwPFS to be 11.4 months (95% CI, 10.1-12.7) in the overall population and 18.2 months (95% CI, 13.9-24.2) in the HRd subgroup. Among the HRd subgroup, the observed median rwPFS was 25.4 months (15.9-not reached) for patients with BRCAm tumors and 14.2 months (95% CI, 8.6-18.6) for those with BRCAwt tumors.

The observed median rwTTNT was 12.4 months (95% CI, 11.5-13.8) in the overall population and 19.6 months (95% CI, 14.9-23.9) in the HRd subgroup. More specifically, the observed rwTTNT was 24.9 months (95% CI, 16.0-not reached) for patients with BRCAm tumors and 15.1 months (95% CI, 10.3-19.8) for patients with BRCAwt tumors.

“Observed median rwPFS and rwTTNT were longer for patients in the HRd subgroup than in the overall population, and specifically longer among those with BRCAm tumors than BRCAwt tumors,” the authors summarized.

Conversely, the researchers acknowledged their study’s limitations, one being that it analyzed US patients primarily seen in the community setting. Therefore, their study may not apply to non-US patients or those treated in academic-based practices. However, the researchers expressed confidence in their findings as they reinforced the PRIMA clinical trial results.

“In this real-world study, among patients with EOC who received 1LM niraparib monotherapy, the observed median rwPFS and rwTTNT were longer for patients in the HRd subgroup and specifically for patients with BRCAm tumors,” the authors wrote. “These results are consistent with results from the PRIMA clinical trial.”

References

1. Salani R, Calderón Boyle TA, Lim J, et al. Real-world outcomes of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer. Future Oncol. Published online January 17, 2025. doi:10.1080/14796694.2024.2441654
2. González-Martín A, Pothuri B, Vergote I, et al. Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023;189:112908. doi:10.1016/j.ejca.2023.04.024