Title :

Mevitem - a phase i/ii of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with sonic hedgehog pathway activation

Author(s) :

Frappaz, Didier [Auteur]
Barritault, Marc [Auteur]
Montane, Laure [Auteur]
Laigle-Donadey, Florence [Auteur]
Chinot, Olivier L. [Auteur]
Le Rhun, Emilie [Auteur]
Bonneville-Levard, Alice [Auteur]
Hottinger, Andreas F. [Auteur]
Meyronnet, David [Auteur]
Bidaux, Anne-Sophie [Auteur]
Garin, Gwenaele [Auteur]
Perol, David [Auteur]

Journal title :

Neuro-Oncology

Abbreviated title :

Neuro Oncol

Publication date :

2021-04-07

ISSN :

1523-5866

Keyword(s) :

medulloblastoma
SMO inhibition
SHH pathway

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BACKGROUND: 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. ...
Show more >BACKGROUND: 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. METHODS: TMZ-naive 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. RESULTS: 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. CONCLUSION: 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Submission date :

2022-06-15T14:00:35Z