MEVITEM-a phase I/II trial of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.

Détails

ID Serval
serval:BIB_CBD0E5E6E601
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
MEVITEM-a phase I/II trial of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.
Périodique
Neuro-oncology
Auteur(s)
Frappaz D., Barritault M., Montané L., Laigle-Donadey F., Chinot O., Le Rhun E., Bonneville-Levard A., Hottinger A.F., Meyronnet D., Bidaux A.S., Garin G., Pérol D.
ISSN
1523-5866 (Electronic)
ISSN-L
1522-8517
Statut éditorial
Publié
Date de publication
02/11/2021
Peer-reviewed
Oui
Volume
23
Numéro
11
Pages
1949-1960
Langue
anglais
Notes
Publication types: Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Vismodegib specifically inhibits Sonic Hedgehog (SHH). We report results of a phase I/II evaluating vismodegib + temozolomide (TMZ) in immunohistochemically defined SHH recurrent/refractory adult medulloblastoma.
TMZ-naïve patients were randomized 2:1 to receive vismodegib + TMZ (arm A) or TMZ (arm B). Patients previously treated with TMZ were enrolled in an exploratory cohort of vismodegib (arm C). If the safety run showed no excessive toxicity, a Simon's 2-stage phase II design was planned to explore the 6-month progression-free survival (PFS-6). Stage II was to proceed if arm A PFS-6 was ≥3/9 at the end of stage I.
A total of 24 patients were included: arm A (10), arm B (5), and arm C (9). Safety analysis showed no excessive toxicity. At the end of stage I, the PFS-6 of arm A was 20% (2/10 patients, 95% unilateral lower confidence limit: 3.7%) and the study was prematurely terminated. The overall response rates (ORR) were 40% (95% CI, 12.2-73.8) and 20% (95% CI, 0.5-71.6) in arm A and B, respectively. In arm C, PFS-6 was 37.5% (95% CI, 8.8-75.5) and ORR was 22.2% (95% CI, 2.8-60.0). Among 11 patients with an expected sensitivity according to new generation sequencing (NGS), 3 had partial response (PR), 4 remained stable disease (SD) while out of 7 potentially resistant patients, 1 had PR and 1 SD.
The addition of vismodegib to TMZ did not add toxicity but failed to improve PFS-6 in SHH recurrent/refractory medulloblastoma. Prediction of sensitivity to vismodegib needs further refinements.
Mots-clé
Anilides/therapeutic use, Cerebellar Neoplasms/drug therapy, Cerebellar Neoplasms/genetics, Hedgehog Proteins/antagonists & inhibitors, Hedgehog Proteins/genetics, Humans, Medulloblastoma/drug therapy, Medulloblastoma/genetics, Pyridines/therapeutic use, Temozolomide/therapeutic use, SHH pathway, SMO inhibition, medulloblastoma
Pubmed
Web of science
Création de la notice
12/04/2021 11:06
Dernière modification de la notice
27/11/2021 6:36
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