503MO - Real-world clinical and genomic characterization of gliomas: Predictive and prognostic insights

Background

Based on our proposal for the first ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) classification for brain tumors [Mirallas et al. ESMO 2022 ] and the descriptive analysis of real-world data in gliomas [Mirallas et al. ASCO 2023 ], we aim to define the clinical actionability of molecular alterations (MA) detected by next-generation sequencing (NGS) in a multicentric glioma cohort.

Methods

Patients (pts) with glioma who had NGS at seven Spanish institutions were included between Jan 2018 and Dec 2022. For predictive associations, pts were classified into Tier1/2, Tier3/4 or wild type (WT) group according to their ESCAT score. Groups were compared using Kruskal-Wallis or Chi-squared tests. To explore prognostic markers, pts with grade 4 glioblastoma (GBM) IDH WT tested within 1 year from diagnosis who had TERT or TP53 genomic results were analyzed. Overall survival (OS) was estimated using the Kaplan-Meier method and Cox hazard ratio were fitted.

Results

Of 580 pts included, 567 pts (98%) underwent NGS testing. A total of 395/567 (71%) had a diagnosis of GBM and 165 (29%) harbored a Tier 1/2 MA. Median age was 51y (IQR: 39-61), 381 (67%) had ECOG ≥1, 223 (40%) were women, and 148 (26%) were 40 or younger. Most common MAs in the entire cohort were PI3KCA (29%), CDKN2A/B loss (28%), EGFR gain (26%), IDH1 (22.4%), EGFRvIII and ATRX (both 17%). Tier 1/2 MAs were more prevalent in younger pts (56% vs 10% in <40y vs >40y), non-GBM (65% vs 9% in non-GBM vs GBM), and TP53 mut (52% vs 24% in mutant vs WT) [all p<0.001]. Meanwhile, Tier 3/4 MAs were more typical for grade 4 gliomas with EGFR MAs (57% vs 2% in WT), TERT mut (55% vs 33% in WT) and CDKN2A/B loss (43% vs 13% in WT) [all p<0.001]. Among pts with grade 4 GBM-IDH WT, 53% had TERT mut and 26% had TP53 mut. In this subset of pts, median OS in case of incomplete resection (R1) was 29.5 months [95%CI 20-40.3] for those with TERT WT and 17 months [95% CI 14-22] in TERT mut pts (p=0.01), but no differences in OS were found in TP53 mut vs WT pts.

Conclusions

Most common actionable MA were IDH, PIK3CA, EGFR, ATRX, suggesting NGS value for identifying potential candidates for targeted treatment. TERT mut was prognostic of worse OS in pts with grade 4 GBM-IDH WT after incomplete tumor resection.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

VHIO.

Funding

Has not received any funding.

Disclosure

O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Institutional, Writing Engagement: Roche, Merck; Other, , Other, Travel Expenses: Kyowa Kirin, Almirall; Other, Travel Expenses and Conference Fee: Sanofi. T. Gorria: Other, Personal, Other, travel expenses: Bristol Myers Squibb, MSD. M.A. Vaz Salgado: Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal and Institutional, Coordinating PI: Pfizer. A. Hernandez Gonzalez: Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Roche, Sanofi; Financial Interests, Institutional, Other, Research Funding: Janssen. M. Gonzalez Rodriguez: Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Roche, AstraZeneca; Financial Interests, Personal, Other, Review clinical cases: Bayer. M. Martinez Garcia: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Takeda, Seagen, Pierre Fabre, Novocure; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer, Daiichi Sankyo, AstraZeneca, Gilead; Non-Financial Interests, Leadership Role, Member of the board: Geino, spanish group of Neuro Oncology; Non-Financial Interests, Principal Investigator, Clinical Trials: Bristol Myers Squibb Celgene, Roche; Non-Financial Interests, Principal Investigator, Clinical trial: Cantargia; Non-Financial Interests, Principal Investigator, Clinical Trial: Laminar Pharma; Non-Financial Interests, Principal Investigator, Clinical trial: Incyte. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Johnson & Johnson, MSD Oncology, Novartis (AAA), Roche, Sanofi; Financial Interests, Institutional, Local PI: Janssen-Cilag International NV, Lilly, S.A, MedImmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A; Other, Member of the Comission: Catalan Program of Ambulatory Medication Comission (CAHMDA). E. Pineda: Financial Interests, Personal, Advisory Board: Novocure. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Foundation Medicine; Financial Interests, Personal, Advisory Board: Bayer, Roche; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinico-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. M. Vieito Villar: Non-Financial Interests, Principal Investigator: Roche, Bristol Myers Squibb, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. All other authors have declared no conflicts of interest.