The hedgehog pathway is implicated in resistance to anticancer therapies in glioblastoma (GB). GEINO1602 (NCT03466450) phase Ib/II study evaluated the safety and efficacy of glasdegib and the Stupp scheme in newly diagnosed GB. Patients received glasdegib with radiotherapy plus concomitant and 6 cycles of adjuvant temozolomide followed by glasdegib monotherapy. The recommended phase 2 dose was 75 mg/day of glasdegib. The primary endpoint was the 15-months overall survival (OS), with a futility threshold of 60% to consider the trial positive; accrual required 70 evaluable patients. 79 patients were enrolled. The 15 m OS rate was 52.1% (95% CI: 41.7-65.2). At 2 years, 29.2% of the patients were still alive. The median progression-free survival (PFS) was 7.1 months (95% CI: 6.2-8.6). Glasdegib plus chemoradiotherapy show preliminary efficacy. Despite not surpassing the futility threshold, 30% lived at the data cutoff. Translational research will help define the molecular traits of long-term survivors.
Salgado et al. (2025) studied this question.