Abstract 1344P
Background
Regular cannabis consumption has been reported at a high frequency in young patients (pts) diagnosed with NSCLC. Their genomic and clinical features may define a unique disease biology. Here, we report molecular characteristics of a cohort of young cannabis smokers with aNSCLC.
Methods
aNSCLC patients aged < 50 years-old who were genotyped at Gustave Roussy between 2019 and 2020 were included in this study if they had a known cannabis consumption, defined as >10 joints/month for ≥ 1 year. Clinical, molecular and radiological data were collected. The presence of actionable genomic alterations (GA) (defined as ESCAT I and II tier), TMB, PD-L1 expression and STK11 mutations were interrogated. Objective response (OR) and progression-free survival (PFS) were determined for pts treated with immune-checkpoint blocker (ICB) with/without chemotherapy.
Results
Out of 100 pts with a molecular profile, 67 had a known smoking status: 26 never smokers, 14 tabacco-only and 27 cannabis-smokers. Cannabis smokers were also tabacco smokers (all, median pack-year 30 [12-30]), 25 were men (93%), median age 44 years [39-48], 23 had adenocarcinoma (82%) and 18 were metastatic at diagnosis (67%), with a median of 3 [2-4] metastatic sites. Targetable GA were found in 5/27 (18.5%) patients: 1 ALK fusion (3.7%), 1 ROS1 fusions (3.7%), 1 HER2 mutation (3.7%) and 2 KRAS G12C mutations (7.6%). KRAS mutations (all subtype) were found in 4/26 (15.3%), while STK11 and TP53 mutations were found in 9/18 (50%) and 17/24 (71%) pts, respectively. Median PD-L1 expression was 0 [0 – 70] and median TMB was 10 mut/Mb [4.52-24.69]. Fourteen pts received single agent ICI or chemo-immunotherapy in the front-line setting. OR were obtained in 6/14 (42.8%). Median PFS was 5.75 months [95% CI: 1.68-9.81].
Conclusions
More than 80% of young cannabis smokers with aNSCLC do not harbor an actionable driver. STK11 mutations have a high prevalence in this population and PD-L1 expression is generally low. Despite high TMB and heavy tabacco smoking, ICB outcomes appear lower than expected in the frontline setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
D. Planchard.
Funding
Has not received any funding.
Disclosure
P. Lavaud: Financial Interests, Personal, Other, Travel, accommodation: Ipsen, Janssen, Mundi Pharma, Astellas-Pharma, AstraZeneca. A. Gazzah: Financial Interests, Institutional, Principal Investigator: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare Ag, BBB Technologies BV, Beigene, Bioalliance Pharma, BioNTech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, Janssen-Cilag, Merck, Novartis, Sanofi; Financial Interests, Personal, Other, Travel: Novartis, Pfizer, Roche, Boehringer. B. Besse: Financial Interests, Personal and Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, Ipsen, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; Financial Interests, Personal and Institutional, Principal Investigator: Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, AbbVie, Loxo Oncology, AstraZeneca, Blueprint Medicines. J-C. Soria: Financial Interests, Personal, Advisory Role: AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, and Takeda; Financial Interests, Personal, Stocks/Shares: AstraZeneca and Gritstone. F. Barlesi: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Seattle Genetics, Takeda. D. Planchard: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Personal, Funding: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. Travel, Accommodation, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. All other authors have declared no conflicts of interest.