# Pooled safety analysis of pimitespib for the treatment of patients with advanced gastrointestinal stromal tumors

## TL;DR

This study analyzed the safety of pimitespib, a drug for advanced gastrointestinal stromal tumors, showing that most side effects are manageable and reversible.

## Contribution

The study provides a pooled safety analysis of pimitespib across multiple clinical trials in Japan.

## Key findings

- Gastrointestinal adverse drug reactions were most common, with diarrhea being the most frequent.
- Most adverse reactions were manageable and resolved over time.
- Ocular adverse reactions occurred in 21.8% of patients, primarily night blindness.

## Abstract

Pimitespib is a first-in-class heat shock protein 90 (HSP90) inhibitor, approved in Japan for the treatment of advanced gastrointestinal stromal tumors (GIST). This study aimed to characterize the incidence and time course of adverse drug reactions (ADRs) associated with pimitespib.

This was a post hoc analysis of pooled safety data from a phase 1 (NCT02965885), phase 2 (jRCT2080223127), and phase 3 (jRCT2080224033) study of pimitespib in patients with advanced GIST. The present analysis included Japanese study participants who received oral pimitespib 160 mg once daily for 5 days followed by 2 days’ rest per week in 21-day cycles. Pooled safety outcomes included the incidence and severity of ADRs; ADRs leading to treatment modifications or discontinuation; and the time to ADR onset and resolution.

In total, 119 patients were included. ADRs were reported in 114 patients (95.8%); gastrointestinal ADRs were most common (99 patients [83.2%]; most often diarrhea [75.6%]) and ocular ADRs occurred in 26 patients (21.8%; most often night blindness [11.8%]). Median time to first onset of any gastrointestinal ADR was 3.0 days; the outcome of gastrointestinal ADRs was recovered/recovering in 61 patients (61.6%), with a median time to resolution of 44.0 days. Median time to first onset of any ocular ADR was 19.0 days; ocular ADRs were recovered/recovering in 20 patients (76.9%), with a median time to resolution of 21.0 days.

This analysis suggests that most ADRs associated with pimitespib are manageable and reversible, thus supporting its use in patients with advanced GIST.