Abstract 290P
Background
The ESMO ESCAT guidelines rank molecular alterations (MA) based on the published evidence supporting their clinical use. Although recommendations have been published for many malignancies, there is a lack of evidence in patients (pts) with pBCs.
Methods
Pts referred for molecular profiling using NGS methods. Clinical actionability was classified using ESCAT; Tier 1 (ready for clinical use), Tier 2 (alteration-drug match associated with antitumor activity, pending quantification of benefit), Tier 3 (supported in other tumor types/similar alterations), and Tier 4 (preclinical evidence). Clinical factors considered for enrichment were diagnosis of glioblastoma (GBM), co-ocurrence of IDH 1/2 mutation (mut), sex, and age ≤40 years. Chi-squared test was used to compare binomial variables.
Results
A total of 160 pts got NGS between Feb 2018 and Dec 2021. Median age was 55 (range 5-75), 40% women, 9% ≤40 at diagnosis, 90% had IDH1/2 wt, and 68% were GBM. The distribution of MA according to ESCAT was: 3 pts had ESCAT 1 alterations (3 BRAFV600E mut). 25 pts had ESCAT 2 alterations (3 PTN loss, 15 IDH1 mut, 4 FGFR3 fusions, 1 FGFR1 mut, 1 IDH2 mut, and 1 FGFR1 mut), 39 pts had ESCAT 3 alterations (34 PTEN mut, 4 PI3KCA mut, 2 ATRX mut), and 37 pts had ESCAT Tier 4 alterations (20 EGFRvIII rearrangements, 10 EGFR amplifications, 10 pTERT mut, and 9 CDKN2A/2B loss). Some pts had concomitant mut, such as IDH1 and 2 mut in Tier 2, explaining the unmatched total. The prevalence in the overall population of Tier 1-2 MA was 17.5% while 47.5% of pts had a Tier 3/4 MA. Potential enrichment factors were as follows: 11% of male pts had a Tier 1-2 MA vs 7% in females (p-value >0.05), 13.3% of pts with a non-GBM had Tier 1-2 vs 5.3% of pts with a primary diagnosis of GBM, and pts with IDH1 mut GBM had a 11.3% of Tier 1/2 MA vs 6.7% of patients with IDH1wt (p-value <0.05).
Conclusions
The prevalence of ESCAT Tier 1-2 alterations is high in pBC suggesting that molecular profiling should be offered. Potential enrichment factors to optimize who should be offered NGS are adults, non-glioblastoma histology, and IDH1 mut subtype.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
VHIO.
Funding
This research has been partially funded by the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (BBVA Foundation) (grant 89/2017). The research leading to these results has received funding from ”la Caixa” Foundation (LCF/PR/CE07/50610001). Cellex Foundation for providing research facilities and equipment. BBVA and La Caixa.
Disclosure
O. Mirallas: Financial Interests, Personal, Invited Speaker: Rovi, Roche, Kyowa Kirin, Grupo Pacifico; Other, Other, Travel Expenses: Kyowa kirin; Other, Travel Expenses and Conference Fee: Sanofi. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Myers Squibb, Roche, Incyte. F.J. Ros Montana: Financial Interests, Institutional, Invited Speaker: Sanofi; Other, Travel and accommodation expenses: Amgen, Pierre Fabre, Merck, Sanofi. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Servier, Sanofi, Roche, Merck Sharp & Dohme, Libbs, Ipsen, Boehringer Ingelheim, Amgen, Lilly, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck. J. Mateo: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Clovis Oncology, Janssen, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Guardant Health, AstraZeneca, Pfizer Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer Oncology; Non-Financial Interests, Institutional, Product Samples, Access to drugs in early development for preclinical testing: AstraZeneca. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daichii Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Avvinity, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc.; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc., BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Invited Speaker, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Invited Speaker, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA-Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc.; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc.; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. E. Garralda: Financial Interests, Personal, Advisory Board: Genentech, F.Hoffmann/La Roche, Neomed Therapeutics1 Inc., Boehringer Ingelheim, Janssen Global Services, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Lilly, Hengrui; Financial Interests, Personal, Invited Speaker: Ellipses Pharma, Seattle Genetics, Bristol Myers Squibb, MSD, F-Star Therapeutics; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis (AAA), Pfizer, Roche, Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV, Laboratoires Leurquin Mediolanum SAS, Lilly, S.A, MedImmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A. All other authors have declared no conflicts of interest.