Efficacy of Pimitespib

Advanced gastrointestinal stromal tumors (GIST) refractory to tyrosine kinase inhibitors (TKIs) have a poor prognosis. A randomized, placebo-controlled Phase III trial evaluated the efficacy and safety of Pimitespib (a novel heat shock protein90 inhibitor) in patients with advanced gastrointestinal stroma refractory to standardTKIs.

Patients with histologically confirmed GIST refractory to imatinib, sunitinib, and regorafenib were randomly divided into a 2:1 group to receive oral pimatinib 160 mg/day or placebo for 5 consecutive days per week for a total of 21 days. Crossover to open-label pimetibi was allowed based on disease progression on blinded central radiology review (BCRR). The primary endpoint was progression-free survival (PFS) by BCRR in all analyzed data sets. Secondary endpoints included overall survival (OS), adjusted using the order-preserving structure failure time (RPSFT) method to reduce the expected confounding effect of crossover.

Eighty-six patients were randomly assigned to receive pimotebib (n=58) or placebo (n=28). Median PFS was 2.8 months [95% confidence interval (CI) 1.6-2.9 months] in the pimetibib group compared with 1.4 months (0.9-1.8 months) in the placebo group [hazard ratio (HR) 0.51 (95% CI 0.30-0.87); one-sided P = 0.006]. Compared with placebo, pimetibib showed improved cross-adjusted OS [HR 0.42 (0.21-0.85), one-sided P=0.007]. Seventeen (60.7%) patients who received placebo crossed over to pimetibib and had a median post-crossover PFS of 2.7 months (95% CI 0.7-4.1 months).