Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial

Abstract

Background Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL. Methods In the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL. Results Patients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01). The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not. Conclusion PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia. Trial registration ClinicalTrials.gov Identifier: NCT03353753; first posted: November 27, 2017.

Efficacy and Safety of Ripretinib in Advanced Gastrointestinal Stromal Tumors within an Expanded Access Program: A Cohort Study

“…Ripretinib is generally well tolerated based on both recorded toxicities [ 5 , 6 ] and, importantly, on patient-reported quality-of-life questionnaires [ 18 , 19 ]. Interestingly, toxicities of grade 3 or higher were less frequent in the BD group.…”

Ripretinib in the treatment of patients with advanced gastrointestinal stromal tumors (GIST)

“…Selfassessment of health status using the VAS EQ-5D-5L questionnaire in patients receiving ripretinib showed an increasing trend, while it decreased in the placebo group [48]. Patients treated with ripretinib assessed their physical functioning as improving, while patients from the placebo group reported its deterioration [48,49]. In summary, patients receiving ripretinib showed a statistically significant improvement in general health and QoL compared to patients receiving placebo, which showed that ripretinib, apart from favorable PFS and OS, also showed a favorable safety profile [48].…”

Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours

“…An additional value of ripretinib is its effectiveness in KIT and PGDFRA wild-type GIST patients [ 82 ]. Ripretinib also resulted in a higher quality of life compared to the placebo (nominal p < 0.01) [ 83 ]. For a subset of patients who progressed in the INVICTUS trial, a dose escalation of ripretinib was allowed (2 × 150 mg daily dose).…”