Abstract
Introduction/Background*Clinical trials consistently demonstrate the detrimental impact of progressive disease (PD) on patients’ health-related quality of life (HRQoL). Progression-free survival (PFS) is an established regulatory endpoint. However, PFS is often excluded as an efficacy endpoint on the basis that — PFS is not patient relevant — in early benefit assessment by select EU health technology agencies. The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) Phase 3 trial showed niraparib significantly prolongs median PFS vs placebo in patients with AOC responsive to 1L platinum (Pt)-based chemotherapy, (CT), regardless of biomarker status. This post-hoc analysis of PRIMA is the first study to examine the relationship between HRQoL and PD in a broad frontline AOC maintenance treatment setting.MethodologyIn PRIMA, patients with AOC responsive to 1L Pt CT were randomised 2:1 to once-daily, maintenance niraparib or placebo. Impact of PD on patient HRQoL, irrespective of treatment, was evaluated within the pooled ITT population by comparing HRQoL at the last on-treatment (pre-progression) visit with HRQoL at end of treatment (EOT), +4 weeks, +8w, +12w, and +24w. Assessments included FOSI, EORTC QLQ-C30, EQ-5D-VAS, and EORTC QLQ-OV28 abdominal/GI symptom scale. ANCOVA was applied with treatment as a fixed effect and HRQoL at last on-treatment visit as a continuous covariate. Mixed models for repeated measurements (MMRM) evaluated cumulative HRQoL changes.Result(s)*Significant reductions in HRQoL from pre- to post-progression were observed across all measures. Compared with pre-progression, FOSI scores (Least-squares mean [95% CI]) were lower at EOT+4w (-2.2 [-2.8, -1.6]) and EOT+24w (-1.7 [-2.3, -1.1]); each p<0.0001. Similarly, at these timepoints EORTC-QLQ-C30 scores were lower by -10.2 (-12.4, -8.0) and -10.7 (13.2, -8.2) points, respectively, and EQ-5D-VAS by -8.2 (-10.4, -6.0) and -6.2 (-8.2, -4.2) points, respectively; each p<0.0001. EORTC QLQ-OV28 scores were significantly worse at EOT+4w (6.6 [4.3, 8.9]) and EOT+24w (5.0 [2.8, 7.2]); each p<0.0001. Similar changes were seen on MMRM analysis.Conclusion*These findings demonstrate HRQoL is negatively impacted by PD in AOC. Preservation of HRQoL, an important therapy goal in the maintenance setting particularly for asymptomatic patients, can be achieved with PFS prolongation. PFS is of significant relevance and clinically important for AOC patients.