Abstract 48P
Background
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) can identify a wide spectrum of genomic alterations (GAs), guiding treatment decisions in patients (pts) with non-small cell lung cancer (NSCLC), especially with adenocarcinoma histology. However, the clinical utility of NGS in pts with lung squamous cell carcinoma (L-SCC) remains controversial. We report the clinical utility of ctDNA-based NGS in a cohort of advanced L-SCC, according to the ESMO ESCAT scale of actionability.
Methods
This was a multicenter retrospective study including treatment-naïve pts with advanced L-SCC with plasma ctDNA NGS performed (InVisionFirst-Lung®) between Feb 2018 and Dec 2022. Clinical actionability was classified according to the ESCAT scale; Tier I (ready for clinical implementation), Tier II (alteration-drug match with antitumor activity), Tier III (supported in other tumor types/similar alterations), and Tier IV (preclinical evidence). We defined clinically informative results as ESCAT tier I/II/III.
Results
A total of 131 pts with advanced L-SCC underwent NGS-ctDNA at 13 institutions in the United States, Canada, France, and Spain. Median age was 73 (range, 45-97), and 2/3 were male. Smoking history data was not available. At diagnosis, ≥1 ctDNA GA was detected in 68% (87/128; 3 failed); TP53 mutation (mut) was the most frequent GA (48%). NGS-ctDNA provided clinically informative results for 33 pts (26%); 5 (4%) were ESCAT tier I (2 BRAFV600E mut, 1 ALK fusion, 1 EGFR exon (ex) 19 deletion, 1 MET ex14 skipping mut), 3 (2%) ESCAT tier IIB (1 KRASG12D mut, 1 KRASG12V mut, 1 KRASG12R mut) and 25 (20%) ESCAT tier III (9 PIK3CA mut, 6 FGFR1 amplifications, 5 EGFR amplifications, 2 KRASG12A mut, 1 IDH1 mut, 1 HRAS mut, 1 NRAS mut). Additionally, NGS-ctDNA detected GAs classified as ESCAT IV (7 CDKN2A mut, 4 PTEN mut, 2 KRAS G13C mut, 1 KRAS G61K mut) in 14 pts (11%).
Conclusions
NGS-ctDNA provided clinically informative results for 26% of pts with advanced lung SCC, including 6% for whom targeted therapies are available in routine practice or clinical trials (4% ESMO ESCAT tier I and 2% ESMO ESCAT tier IIB). These results suggest that molecular profiling, including plasma NGS testing, should be considered in this population.
Legal entity responsible for the study
Neogenomics.
Funding
Has not received any funding.
Disclosure
M. García Pardo de Santayana: Financial Interests, Personal and Institutional, Research Grant, SEOM "Retorno de Investigadores" Grant: SEOM; Financial Interests, Personal and Institutional, Research Grant, AECC "Ayuda Clinico Junior 2023" Grant: AECC. M. Nahorski: Financial Interests, Personal and Institutional, Full or part-time Employment: Neogenomics. K. Howarth: Financial Interests, Personal, Full or part-time Employment: SAGA diagnostics. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Invited Speaker, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Invited Speaker, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee ChairPast Fellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020-2022Past President 2023-2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assesmment for lung cancer screening evaluation: EUnetHTA; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS); Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Non-Financial Interests, Personal, Other, Educational Committee Member: IASLC; Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with TEVA: TEVA. C. Teixido: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharp & Dohme, Roche Farma, Diaceutics, Pfizer, Janssen Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Novartis. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Boehringer, Pfizer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen, Novartis, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Amgen, Novartis, Sanofi, Merck; Financial Interests, Personal, Expert Testimony: Merck, Janssen; Non-Financial Interests, Personal, Principal Investigator, PI of Investigator Initiated Trial (PEERS) sponsored by MSD. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Sanofi, Janssen. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal Therapeutics. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda, Janssen. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, Roche, AstraZeneca, MSD, Janssen; Financial Interests, Personal, Invited Speaker: Takeda, Roche, BMS, AstraZeneca, Janssen; Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI; Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS; Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen; Financial Interests, Institutional, Invited Speaker, Cover cost of molecular test.: INIVATA; Financial Interests, Institutional, Invited Speaker: GILEAD; Financial Interests, Institutional, Invited Speaker, Beca SEOM Grupo Emergente 2022: AstraZeneca. All other authors have declared no conflicts of interest.