First-Line Niraparib Maintenance Is Not Associated With Worse HRQOL in Advanced Ovarian Cancer

Although frontline maintenance therapy with niraparib (Zejula) was associated with an early, transient increase in gastrointestinal (GI) symptoms, patients treated with the PARP inhibitor did not experience a worsening of overall health-related quality of life (HRQOL) compared with those given placebo, according to patient-reported outcomes (PROs) from the phase 3 PRIMA trial (NCT02655016).¹

Findings published in Gynecologic Oncology found that PRO adherence rates remained above 80% across all instruments and all time points throughout the trial for patients in the niraparib arm (n = 487) and the placebo arm (n = 246). The least squares (LS) mean change from baseline scores for global health/overall QOL and physical function were similar between the niraparib and placebo arms, and they generally remained consistent over time.

For global health/overall QOL, the LS mean score at baseline was 71.5 in the niraparib arm (n = 478) compared with 70.2 in the placebo arm (n = 243). At cycle 18, the LS mean scores were 77.0 with niraparib (n = 102) and 73.5 with placebo (n = 38). Regarding physical function, the LS mean scores in the niraparib arm at baseline (n = 479) and at cycle 18 (n = 101) were 81.0 and 86.2, respectively. In the placebo arm, those scores were 78.7 at baseline (n = 244) and 83.7 at cycle 18 (n = 38).

“There was a slight downward trend in niraparib-treated patients for fatigue LS mean change from baseline scores from cycle 3 to cycle 18, indicating symptom improvement,” lead study author Bhavana Pothuri, MD, and colleagues, wrote. “Placebo LS mean change from baseline scores [for fatigue] remained consistent through cycle 18 and showed no difference compared with niraparib. Symptom LS mean change from baseline scores for pain were generally similar across treatment arms through cycle 18.”

Pothuri is a professor in the Department of Obstetrics and Gynecology, as well as in the Department of Medicine, at New York University Grossman School of Medicine. She is also the director of Gynecologic Oncology Research, medical director of the Clinical Trials Office, and director of Gynecologic Oncology Clinical Trials at Perlmutter Cancer Center in New York, New York.

Notably, findings from the PRO analysis also showed that LS mean change from baseline scores for GI symptoms, including nausea/vomiting, appetite loss, and constipation, were higher in patients treated with niraparib vs those given placebo. These differences occurred primarily during early treatment, and differences between treatment arms resolved after cycle 9 for nausea/vomiting and after cycle 5 for appetite loss.

In April 2020, the FDA approved niraparib for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status. The regulatory decision was supported by prior data from PRIMA.²

The randomized, double-blind, placebo-controlled, multicenter study included patients with histologically diagnosed stage III/IV high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer per International Federation of Gynecology and Obstetrics staging.¹ Patients were required to have a partial response (PR) or complete response (CR) after at least 6 and no more than 9 total cycles of frontline, platinum-based chemotherapy.

Enrolled patients were randomly assigned in a 2:1 fashion to receive maintenance niraparib or placebo once per day in 28-day cycles until progressive disease or unacceptable toxicity. The primary end point was progression-free survival, and secondary end points included overall survival, time to first subsequent therapy, time to second progression, PROs, and QOL.

HRQOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QOL Questionnaire Ovarian Cancer module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy–Ovarian Symptom Index (FOSI), and the EQ-5D-5L.

In the HRQOL analysis, LS mean change was used to evaluate PROs over time, and results were reported through cycle 18 of treatment with a median follow-up of 13.8 months in the overall population. LS mean change from baseline was estimated with a mixed-effects model for repeated measures to account for data variability.

“Consistent with the known safety profile of niraparib, [patients treated with] niraparib self-reported worse GI symptoms than [patients treated with] placebo on the EORTC QLQ-C30 [for nausea and vomiting, appetite loss, and constipation],” study authors wrote. “Except for constipation, the worsening did not meet the threshold for minimal clinically important difference [± 10-point change] and was temporary, with the differences between treatment arms resolving after cycle 9.”

The study authors noted that although PROs were prespecified in the study plan, the trial was not powered to detect differences in PRO end points between the 2 arms. They also explained that PRIMA enrolled a patient population that was highly selective, meaning that the results from the study may not be generalizable to the overall population of patients with ovarian cancer.

“PRO data collected during the PRIMA trial shows that while there was a transient increase in self-reported GI symptoms early during treatment, niraparib maintenance therapy did not adversely affect overall HRQOL of patients with ovarian [cancer who] had a CR or PR to platinum-based chemotherapy. These data support that niraparib is a well-tolerated option for first-line maintenance therapy in patients with ovarian cancer,” study authors concluded.

References

1. Pothuri B, Han S, Chase DM, et al. Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial. Gynecol Oncol. 2024;184:168-177. doi:10.1016/j.ygyno.2024.01.021
2. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. FDA. April 29, 2020. Accessed March 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer