Toxicity profile and discordance between patients/physicians regarding niraparib maintenance in recurrent ovarian cancer (ROC) patients: Lessons from the NIQOLE real-life study—GINECO study.
Authors: Joly Florence , Kalbacher Elsa , Decoopman Delphine Garbay , Ouldbey Yaelle , Follana Philippe , Dawood Heba , Legouffe Eric , Brachet Pierre-Emmanuel , Spaeth Dominique , Combe Pierre , Hardy-Bessard Anne-Claire , Selle Frédéric , Grenier Julien , Lebreton Coriolan , Derbel Olfa , Bouheret Paul , Fournel Pierre , Fernandez Diez Yolanda , Quesada Stanislas , Kurtz Jean Emmanuel 
Published: June 2023

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Background: Niraparib (NI) maintenance is a standard of care in platinum-sensitive ROC. Based on pivotal randomized trials, toxicity profile appears manageable through adapted drug dosing. However, data on tolerance and feasibility for unselected patients (pts) are missing, especially regarding pts’ reported adverse events (AE). Methods: NIQOLE study is a real-life longitudinal multicenter, phase IV study in ROC pts treated with NI maintenance. NI starting dose was adapted to pts’ weight and platelet count. The primary endpoint was to describe physicians’ reported AE (NCI-CTC-AE, grading from 0 to 5) leading to treatment modifications (TM), defined by dose reduction or treatment interruption/discontinuation from baseline to month 3 and delay of first TM. Secondary endpoints included duration of treatment and pts’ reported AE. Progression rates were exploratory endpoints. Owing to a digital device, pts provided remoted weekly AE (NCI PRO-CTC-AE, grading from 0 to 3) which were accessible to investigators. Concordance between the main symptomatic AEs reported by pts and those reported by physicians was analyzed. Results: 139 pts were treated: median age 70 [44-88], high-grade serous histology 91%, BRCA mutation 5%, first relapse 72%, prior bevacizumab 71%. The median delay from platinum-based regimen and NI was 49 days [15-109]. NI starting dose was 200 mg in 80% of pts and the median treatment duration was 5.6 months [0.2-21]. Progression rates at 3 and 6 months were 19 and 45%, respectively. At 3 months, 60% (n=84%) of pts had at least one TM, of whom 47% (n=66) were treatment-related AEs: dose reduction in 17/66 (26%), interruption in 53/66 (80%) and discontinuation in 11/66 (17%). The first AE inducing TM occurred at 22 days (median) [2 -91]. Thrombocytopenia was the main AE leading to TM (70% of cases). 24% of AEs were grade 3-4. Remoted PRO-CTC-AEs were acknowledged by physicians in 59% of cases of whom 31% led to adaptation of pts’ care. During the 3 months, 98% of pts reported symptomatic AEs (including nausea, constipation, fatigue, dry mouth and insomnia), of which 66% were grade 3. There was a very poor correlation (<0.20) between symptomatic AEs reported by the pts vs by the physicians (table). Conclusions: In real life, despite initial individual dosing, NI maintenance requires frequent TM during the first 3 months of treatment. There is a strong discrepancy between symptomatic AEs regularly captured by pts and those reported by physicians during clinics. Next generation of clinical trials should integrate pts' perspective to better assess toxicity and manage treatment course. Clinical trial information: NCT03752216 . [Table: see text]