Methods: Patients over 16 years with PROS and PIK3CA pathogenic variants were included in a phase IB/IIA multi-centre, open-label single arm trial (Six patients at 1mg/day of taselisib, then 24 at 2mg/day).
The primary outcome was the occurrence of dose limiting toxicity (DLT). Efficacy outcomes were the relative changes after treatment of i) tissue volume at affected and unaffected sites, both clinically and on imaging, ii) cutaneous vascular outcomes when relevant, iii) biologic parameters, iv) quality of life and v) patient-reported outcomes.
Results: Among 19 enrolled patients, 2 experienced a DLT (enteritis and pachymeningitis) leading to early trial termination (17 treated, 10 completed the study). No serious adverse reaction occurred in the 1mg cohort (n=6). No significant reduction in affected tissue volume was observed (mean -4.2%; p=0.81; SD 14.01). Thirteen (76.4%) participants reported clinical improvement (pain reduction, chronic bleeding resolution, functional improvement).
Conclusion: Despite functional improvement, the safety profile of low-dose taselisib precludes its longterm use.
- clinical trial
- Overgrowth syndrome
- PROS treatment