3522 - Precision medicine for patients with primary brain tumors: Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trial

Background

Primary brain tumors are highly heterogeneous and current therapy confers only modest clinical benefit. There is a tremendous need for new therapeutic options and genomic profiling could help defining new strategies.

Methods

Data from patients with advanced primary brain tumors enrolled in the prospective clinical trial MOSCATO at the Drug Development Department (DITEP) at Gustave Roussy Cancer Center were retrospectively reviewed. Multiple high throughput molecular techniques were used to identify genetic mutations: Next Generation Sequencing (NGS), comparative genomic hybridization array (CGHa) and Foundation one CDx (FMI). Matched therapy was decided accordingly for patients who had targeted molecular alterations.

Results

Between April 2016 and December 2018, 103 patients with primary brain tumors were enrolled. Median age was 48 years (range, 19-75), median number of previous systemic therapies was 2 (range, 0–5), 98% had an ECOG performance status 0 or 1. The most prevalent histology was glioblastoma (70 %). Ten patients were screen failure due to unavailability of tumor tissue and no possibility of new brain biopsy. Eighty-nine molecular analyses were successful (CGH: N = 45, NGS: N = 47, FMI: N = 42). Median time between consent and results was 49 days (range, 18-235). Tumor mutational burden (TMB) was available in 42 pts and was considered low (<6) in 33 patients. Altogether, 365 actionable alterations were detected: amplification (n = 82; 22.5 %), deletion (n = 76; 21%), mutation (n = 197; 54 %) and rearrangement (n = 10 ; 2.7 %). Most frequent alterations were: CDKN2A/2B (10%), EGFR (9.1%), TP53 (8.6%), TERT p (7.4%), PTEN (6.8%). Thirty patients (34%) were oriented to a matched therapy according to actionable alterations, five of them being treated with targeted therapies (BRAF inhibitor; n = 1, EGFR inhibitor; n = 1, mTOR inhibitor; n = 1, FGFR inhibitor; n = 1, TKI-VEGFR n = 1).

Conclusions

Molecular profiling in patients with primary brain tumors is feasible and can lead to orientation in clinical trials and/or treatment with targeted therapies. However the reasons for the small number of patients finally treated are currently under investigations and will be presented at the conference.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Christophe Massard.

Funding

Institut Gustave Roussy.

Disclosure

C. Baldini: Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Abbvie; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Sanofi. L. Verlingue: Speaker Bureau / Expert testimony: Adaptherapy; Speaker Bureau / Expert testimony: Pierre Fabre; Research grant / Funding (self): BMS. E. Angevin: Advisory / Consultancy: Merck; Advisory / Consultancy: GSK; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Abbvie; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Pfizer. A. Varga: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Astra Zeeneca; Speaker Bureau / Expert testimony: MSD. S. Postel Vinay: Research grant / Funding (self): Merck; Research grant / Funding (self): Boehringer; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: AstraZeneca. A. Gazzah: Travel / Accommodation / Expenses: Boehringer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis. R. Bahleda: Travel / Accommodation / Expenses: Taiho; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Boehringer. A. Marabelle: Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Onxeo; Advisory / Consultancy: EISAI; Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Genticel; Advisory / Consultancy: Rigontec; Advisory / Consultancy: Diachii; Advisory / Consultancy: Imaxio; Advisory / Consultancy: Sanofi; Advisory / Consultancy: BioNtech; Advisory / Consultancy: Corvus; Advisory / Consultancy: Deerfield; Advisory / Consultancy: Bioncotech; Research grant / Funding (self): Merus; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer; Research grant / Funding (self): Transgene. V. Ribrag: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Nanostring Technologies; Speaker Bureau / Expert testimony: Servier; Honoraria (self): Eisai. S. Champiat: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Janssen. J. Michot: Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Janssen. A. Hollebecque: Advisory / Consultancy: Amgen; Advisory / Consultancy: Spectrum Pharmaceuticals; Advisory / Consultancy: Lilly; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Lilly; Speaker Bureau / Expert testimony: Bayer. J. Soria: Full / Part-time employment: Medimmune. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Beigene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Lilly; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Medimmune; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.