Abstract 702P
Background
There is no conventional therapy approved for R/M SGTs. The current use of sequencing techniques has demonstrated that SGTs have a low mutational burden with recurrent mutations in epigenetic modifiers, opening up a range of therapeutic options with epigenetic targeted agents (ETAs).
Methods
We analyzed R/M SGTs pts with a hybrid capture panel including epigenetic modifiers treated at the Vall d´Hebron Hospital from 2016 to 2022 (HCP-NGS). The status of genomic aberrations of genes encoding epigenetic regulators (epigenetic genes) and patients responses to ETAs were correlated with outcomes. Overall response rate (ORR) was evaluated with RECIST 1.1 criteria. Progression-free survival (PFS) and Overall Survival (OS) were calculated with Kaplan-Meier estimates.
Results
Among 51 pts characterized with HCP-NGS, 16 were identified with genomic mutations in epigenetic genes (5 in the genes encoding subunits of SWI/SNF, 6 in genes encoding chromatin, 5 in genes involved in the DNA methylation process, and 10 in others). No difference in OS from diagnosis was observed between patients with or without mutations in epigenetic genes; pts with mutations in epigenetic genes: mOS 237 months (mo) [95% CI 113.3 mo-not-reached]. Pts without mutations in epigentic genes: mOS not-reached (95% CI 81.5 mo-not reached), p= 0.4 log-rank test. Seventeen pts were treated with ETAs: 6 of them (35.29%) had mutations in epigenetic genes (matched) and 11 (64.70%) did not (unmatched). In the matched pts, mPFS with ETAs was 18.8 mo (95% CI 7.96-not reached); there were no responses, 5 pts had stable disease (4 of them for >12 mo), and 1 pt had progressive disease. In the unmatched pts, PFS with ETAs was 10.2 mo (95% CI 7.83-NR) (p= 0.8 log-rank test), 1 had a partial response, and 10 had stable disease (4 of them for >12 mo).
Conclusions
Overall, genomic alterations in epigenetic regulators identified by HCP-NGS were not statistically associated with better outcomes with ETAs in this small cohort of patients. Further analysis of genomic alterations matched with corresponding ETAs is required.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
La Caixa Foundation - Institutional grant: LCF/PR/CEO7/50610001; Cellex Foundation: Institutional grant.
Disclosure
M.A. Rezqallah Aron: Financial Interests, Institutional, Invited Speaker: Pfizer. J.D. Assaf Pastrana: Financial Interests, Institutional, Research Grant, Clinical trial PI: Merck-Sharp-Dome. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Merck Serono, Peptomyc, F. Hoffmann-La Roche, Novartis, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, Takeda, Touchoncology; Financial Interests, Institutional, Other, Grant For Oncology Innovation: Merck Healthcare KGAa; Financial Interests, Institutional, Other, Fundación Merck Salud: Fundación Merck Salud; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). 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. I. Brana: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. All other authors have declared no conflicts of interest.