Fiche publication
Date publication
mars 2026
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MALOUF Gabriel
Tous les auteurs :
Gounder M, Schöffski P, Jones RL, Stacchiotti S, Demetri GD, Cote GM, Agulnik M, Chugh R, Jahan T, Gupta AA, Chen TW, Ratan R, Dileo P, Drilon A, Malouf GG, Szanto A, Gupta N, Tannir NM
Lien Pubmed
Résumé
Advanced tumors harboring SWI/SNF mutations are rare and aggressive. Often presenting in young patients, treatment options are limited. This phase II basket study (NCT02601950) assessed oral tazemetostat, an EZH2 inhibitor, at 800 mg twice daily (N = 129). Cohorts included malignant rhabdoid tumors (n = 32, Cohort 1), synovial sarcoma (n = 33, Cohort 2), INI1-negative tumors (n = 32, Cohort 3), renal medullary carcinoma (n = 14, Cohort 4), and poorly differentiated chordoma (n = 18, Cohort 7). Efficacy assessments used a 2-stage Green-Dahlberg design. Stage 1 futility was predefined as objective responses (complete/partial [CR/PR]) <5% (Cohorts 1, 3, 4, 7) or 16-week progression-free survival (PFS) <15% (Cohort 2). Sufficient clinical activity was declared in Stage 2 if ≥5 patients had a CR/PR (Cohorts 1,3,4,7) or ≥9 patients had a CR/PR, or stable disease (Cohort 2; primary endpoints). Responses were observed in malignant rhabdoid tumors (9%; n = 2 PR, n = 1 CR), INI1-negative tumors (9%; n = 3 PR, n = 0 CR), and poorly differentiated chordoma (6%; n = 1 PR, n = 0 CR) but not the remaining 2 cohorts (both 0%). 16-week PFS for synovial sarcoma was 15.2% (n = 5). Grade ≥3 treatment-related adverse events occurred in 10% of patients. Tazemetostat demonstrated preliminary antitumor activity in a subset of poor-prognosis cancers, underscoring the need for combination strategies when EZH2 signaling is not the sole disease driver.
Référence
Nat Commun. 2026 03 25;:
