Quality-of-life outcomes with pimitespib in patients with advanced gastrointestinal stromal tumor: results from the randomized, double-blind, placebo-controlled, phase III, CHAPTER-GIST-301 study

BACKGROUND: Health-related quality of life (HRQoL) has emerged as an important outcome following the introduction of tyrosine kinase inhibitors for metastatic gastrointestinal stromal tumors (GISTs). We report the HRQoL results from the randomized, placebo-controlled, phase III CHAPTER-GIST-301 study evaluating pimitespib as fourth-line therapy for metastatic GIST. PATIENTS AND METHODS: HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30) v3.0 and EuroQol Five Dimensions Questionnaire-5L (EQ-5D-5L) at baseline and scheduled study visits during the blinded period. Between-group change from baseline scores were compared using a mixed model repeated measure model. The percentage of patients with a clinically meaningful deterioration (≥10 point change from baseline) in HRQoL was calculated for each EORTC QLQ-C30 item. Time to deterioration (TTD) was calculated using the Kaplan-Meier method. RESULTS: Overall, 86 patients were randomized to receive pimitespib (n = 58) or placebo (n = 28) in the CHAPTER-GIST-301 study. Compliance across all HRQoL questionnaires exceeded 80% by week 18. Least-squares mean changes from baseline were generally similar between pimitespib and placebo treatment groups, with the exception of diarrhea and appetite loss. Items associated with a ≥10 point difference in EORTC QLQ-C30 were diarrhea (hazard ratio 4.82, 95% confidence interval 2.17-10.71), with almost no difference in other items. CONCLUSION: Pimitespib as a new treatment option in the fourth-line setting did not negatively impact HRQoL overall, with the exception of diarrhea and appetite loss, in patients with metastatic GIST.