Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial
Maria-Pilar Barretina-Ginesta 1 , Bradley J Monk 2 , Sileny Han 3 , Bhavana Pothuri 4 , Annika Auranen 5 , Dana M Chase 2 , Domenica Lorusso 6 , Charles Anderson 7 , Sophie Abadie-Lacourtoisie 8 , Noelle Cloven 9 , Elena I Braicu 10 , Amnon Amit 11 , Andrés Redondo 12 , Ruchit Shah 13 , Nehemiah Kebede 14 , Carol Hawkes 15 , Divya Gupta 16 , Tatia Woodward 17 , David M O'Malley 18 , Antonio González-Martín 19
Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo.
Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019).
Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9-8.9] and 4.1 [95% CI, 2.2-5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5-8.6] and 3.5 [95% CI, 1.7-5.6] months, respectively) in the HRd and ITT populations.
Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure.
Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016.