Abstract
New ESMO scale for clinical actionability of molecular targets (ESCAT) for gliomas based on a multicentric real world data cohort using next-generation sequencing (NGS).
Author
Oriol Mirallas
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain
info_outline
Oriol Mirallas, Gabriel Velilla, Fiorella Ruiz-Pace, Jesús Yaringaño, Ainhoa Hernandez Gonzalez, Daniel Lopez Valbuena, Diego Gómez-Puerto, Teresa Gorria, Maria Ángeles Vaz, Marta Doménech, Alvaro Martinez-Monino, Macarena González, Maria Castro, María Martínez-García, Estela Pineda, Joan Carles, Rodrigo Dienstmann, Carmen Balana, Juan Manuel Sepulveda Sanchez, Maria Vieito
Full text
Authors
Oriol Mirallas
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain
info_outline
Oriol Mirallas, Gabriel Velilla, Fiorella Ruiz-Pace, Jesús Yaringaño, Ainhoa Hernandez Gonzalez, Daniel Lopez Valbuena, Diego Gómez-Puerto, Teresa Gorria, Maria Ángeles Vaz, Marta Doménech, Alvaro Martinez-Monino, Macarena González, Maria Castro, María Martínez-García, Estela Pineda, Joan Carles, Rodrigo Dienstmann, Carmen Balana, Juan Manuel Sepulveda Sanchez, Maria Vieito
Organizations
Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain, Hospital Universitario 12 de Octubre, Madrid, Spain, Oncology Data Science (ODysSey) Group, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron University Hospital, Barcelona, Spain, Institut Catala d'Oncologia Badalona; Applied Research Group in Oncology (B- ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Badalona Barcelona, Spain, Hospital Clinic-DIBAPS, Barcelona, Spain, Medical Oncology Department, Ramon y Cajal University Hospital, Madrid, Spain, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, IGTP. Medical Oncology, Badalona, Spain, Hospital del Mar, Barcelona, Spain, Hospital Universitari Vall d'Hebron, Barcelona, Spain, Medical Oncology Department, Hospital Clínic de Barcelona, Barcelona, Spain, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Hospital Germans Trias i Pujol. ICO Badalona, A Gudiña, Spain, Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain
Abstract Disclosures
Research Funding
Institutional Funding
VHIO
Background:
The ESMO ESCAT scale rank molecular alterations (MA) based on the published evidence supporting their clinical use. Building on our proposal for the first ESCAT classification for primary brain tumors (pBT) [Mirallas
et al.
ESMO 2022], we aim to describe the clinical actionability of NGS in a multicentric glioma cohort and gather clinical factors that enrich patients with MA to justify performing NGS.
Methods:
A multicentric retrospective study included pts with molecular profiling using NGS methods (Foundation Medicine, local NGS, Caris, Oncomine,
and fusion panels). Clinical actionability was classified using the ESCAT scale; Tier 1 (ready for clinical implementation), Tier 2 (alteration-drug match with antitumor activity), Tier 3 (supported in other tumor types), and Tier 4 (preclinical evidence). Clinical factors considered for enrichment were diagnosis of glioblastoma (GBM), sex, and age ≤40 years, differences between groups were determined using Chi-squared test. The overall survival (OS) was calculated through Kaplan-Meier method and cox hazard ratio were fitted.
Results:
A total of 361 pts with NGS performed between Feb 2018 and Dec 2022 at 4 hospitals in Spain. Median age was 51.5 (range, 3.3-83.8), 77% had ECOG ≥1, 39.2% were women, 23.4% were 40 or younger, 20.8% had IDH1mut, and 73.5% had a diagnosis of GBM. The distribution of MA according to ESCAT was: 10 pts ESCAT 1 (5 BRAFV600E mut, 5 NTRK 1-3 fusions); 75 pts ESCAT 2 (67 IDH1 mut, 6 FGFR-TACC rearrangement, 4 FGFR 1-3 mut, 3 IDH2 mut); 105 pts ESCAT 3 (98 PIK3CA/PTEN mut, 12 PTEN loss, 11 H3K27M mut, 6 BRAF fusion, 2 MET mut, 1 FGFR3 amplification); 93 pts ESCAT 4 (119 TERT mut, 77 EGFR gain, 67 CDKN2A loss, 58 CDKN2B loss, 48 EGFRvIII rearrangement, 46 ATRX mut, 40 EGFR mut, 8 ATM mut). Prevalence of Tier 1-2 MA was 23.6%. In relation to enrichment factors: 12% >40y pts had ESCAT1-2 vs 61% in ≤40y (p<0.001), pts with GBM had a 11% prevalence vs 61% non-GBM (p<0.001), and non-gender differences were seen. The median OS for Tier 1-2 was 135 months (95% CI 166-99) vs Tier 3-4 of 24 months (95% CI 21.5-29.6). Significantly worse OS was observed for Tier 3-4 gliomas (HR: 4.11; 2.84-5.95, p<0.001), and remained significant after adjusting for histology and hospital center (p<0.01).
Conclusions:
The prevalence of ESCAT Tier 1-2 alterations is high in gliomas suggesting that molecular profiling should be offered, at least, in tertiary centers where these techniques are available. Potential enrichment factors to offer NGS were age and non-GBM pBT, but not gender.
16 organizations
1 product
20 drugs
5 targets
Organization
Hospital Universitario 12 de OctubreOrganization
Vall d´Hebron Institute of Oncology (VHIO)Organization
Institut Catala d'Oncologia BadalonaOrganization
Hospital Clinic-DIBAPSOrganization
Ramon y Cajal University HospitalOrganization
Catalan Institute of Oncology-HospitaletOrganization
Hospital Germans Trias i PujolOrganization
Hospital del Mar, Barcelona, SpainOrganization
Hospital Clínic de Barcelona, IDIBAPSOrganization
Medical Oncology ServiceDrug
BRAFV600EDrug
NTRNK 1-3Drug
IDH1Drug
FGFR-TACCDrug
FGFR 1-3Drug
IDH2Drug
PIK3CA/PTENDrug
PTENDrug
H3K27MDrug
BRAFProduct
TMZDrug
FGFR3Drug
TERTDrug
CDKN2A/BDrug
CDKN2BDrug
NTRK 1-3Drug
CDKN2BDrug
EGFRvIIIDrug
ATRXDrug
ATMTarget
ATRXTarget
ATMTarget
CDKN2BTarget
NTRK 1-3Target
EGFRvIII