Abstract 686P
Background
Immunotherapy has changed the treatment of HNSCC pts since the introduction of immune checkpoint inhibitors (ICI). Genomic instability increases neo-antigen production, which has been related with sensitivity to IO. We investigated whether single-gene alterations in TP53, cell-cycle and other mutations (mut) or copy number gains (CNG) predict outcomes in R/M HNSCC pts treated with IO.
Methods
Review of a retrospective database of R/M HNSCC pts treated with IO at VHIO from 2014-2021 was conducted. NGS panel in FFPE prior to ICI was performed in-house, which analyzed 61 genes, or OncoDNA, which analyzed over 400 genes. Clinical data and laboratory parameters were collected, and the prognostic nutritional index (PNI) was calculated. Patients who received chemotherapy were excluded. The primary endpoints were PFS and OS calculated with the Kaplan-Meier method, and univariate and multivariable Cox models were fitted.
Results
Out of 116 pts treated with IO, median age was 64 years, 94% ECOG ≤ 1, 48 pts (41%) were treated with single agent and 73 pts (63%) in the second-line or beyond. Median follow-up was 39.5 months (m) with a median PFS of 3 m (1.91-4.9) and a median OS of 12.56 m (CI95% 9-21). Baseline NGS was available from 73 pts: 44 (60.3%) were TP53 mut, 12 (16.4%) had cell-cycle alterations, 5 PI3KCA mut (6.8%), and 3 HRAS mut (4.1%). TP53 mut were not associated with PFS nor OS in our cohort (p>0.05). Contrary, cell-cycle alterations were significantly associated with worse PFS (HR: 1.86; p=0.04), but not with OS (p=0.07). CNG were found in 18 pts; 10 (55%) CCND1, 2 (11%) EGFR and 1 MYC, HER2, MDM2, ATM, FGFR1, and TERT. PFS was significantly worse in the presence of any CNG (HR=2.33; p=0.01). In a multivariable model including age, PNI, and LDH the presence of CNG remained an independent prognostic factor (HR: 2.51; 95% CI 1.1-5.7, p=0.026).
Conclusions
Cell-cycle alterations were associated with a worse PFS in R/M HNSCC pts treated with IO. The strongest molecular alteration related to PFS was copy number gain. Despite prospective studies must be performed, these results suggest that NGS may help predict those pts who will benefit from IO.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d'Hebron Institute of Oncology.
Funding
Vall d'Hebron Institute of Oncology.
Disclosure
O. Mirallas: Financial Interests, Personal, Invited Speaker: Rovi, Roche, Kyowa Kirin, Grupo Pacifico; Other, Travel Expenses: Kyowa kirin; Other, Travel Expenses and Conference Fee: Sanofi. 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. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristrol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono; 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 Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). 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, Debiopharm, Janssen Oncology, Kura, Merck Serono, 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.