OBJECTIVES: Ripretinib is FDA-approved as a fourth-line therapy in unresectable GIST and is the only NCCN-recommended therapy. In the INVICTUS study, an international, multicenter, randomised, double-blind, placebo-controlled Phase 3 trial, ripretinib was shown to be an effective, and well-tolerated inhibitor of KIT and PDGFRA primary and secondary mutations, delaying disease progression in unresectable advanced 4L GIST. Ripretinib patients reported being able to maintain quality of life (QoL), health, and physical and role functioning in the INVICTUS study, while these measures declined sharply in the placebo arm. The average difference between the two arms was both clinically and statistically significant. Here, we provide further insight into outcomes at the patient level.

METHODS: PROs were assessed using the EQ-5D-5L visual analogue scale (VAS) and questions from the EORTC QLQ C30 (physical function, role function, overall self-reported health, and overall QoL). Definitive deterioration (DD) was defined as a clinically meaningful decline in the PRO measure that does not recover. TUDD was analysed for VAS individually and for two joint measures: physical and role functioning, and health and QoL. For the joint variables, DD must occur in both components. Results are presented as Kaplan-Meier survival curves.

RESULTS: Patients on ripretinib had longer time until DD in each of functioning, health and QoL, and VAS than placebo. Patients on placebo reported DD within a median 8 weeks, while the median time until TUDD in overall health was not reached for patients on ripretinib. For the physical and role functioning, and the VAS, the TUDD was 41.6 weeks.

CONCLUSIONS: In this heavily pretreated 4L GIST population, QoL is an important aspect of treatment success. For patients on ripretinib, median TUDD was 5 times as long as those on placebo. Median TUDD was not shorter than median PFS, suggesting that tolerability was not a driver of discontinuation.