In young patients diagnosed with non–small-cell lung cancer (NSCLC), regular cannabis consumption has been observed at a high rate. These patients’ genetic and clinical characteristics could help to define a distinct disease biology. A study was performed by analyzing the molecular characteristics of a cohort of young cannabis smokers with advanced NSCLC.
This study included patients with advanced NSCLC aged <50 years who were genotyped at Gustave Roussy, Villejuif, France, between 2019 and 2020 if they had a history of cannabis consumption, defined as >10 joints per month for a year. Data were gathered from clinical, molecular, and radiologic sources. Tumor mutation burden (TMB), PD-L1 expression, and STK11 mutations were investigated for the presence of actionable genomic alterations. Patients who received an immune checkpoint blocker (ICB) with or without chemotherapy had their objective response and progression-free survival determined.1
There were 67 known smokers of 100 patients with a molecular profile: 26 had never smoked, 14 were tobacco-only smokers, and 27 were cannabis smokers. Cannabis smokers were also tobacco smokers, 93% were men with a median age of 44 years, 82% had adenocarcinoma, and 67% had metastatic disease at the time of diagnosis with a median of 3 metastatic locations. A total of 18.5% of patients had genomic alterations that may be targeted: 1 (3.7%) had ALK fusion, 1 (3.7%) had ROS1 fusion, 1 (3.7%) had human HER2 mutation, and 2 (7.6%) had KRASG12C mutations. KRAS mutations were detected in 15.3% of the participants, whereas STK11 and TP53 mutations were found in 50% and 71% of the participants, respectively. The median TMB was 10 mut/Mb (range, 4.52-24.69 mut/Mb) and the median PD-L1 expression was 0 (range, 0-70). In the frontline context, 14 patients received single-agent ICB or chemo-immunotherapy. In 42.8% of cases, objective response was acquired. Progression-free survival was 5.75 months on average.1
More than 80% of young cannabis consumers with advanced NSCLC did not have a detectable driver. In this population, STK11 mutations are common, whereas PD-L1 expression is often low. ICB effects appear to be lower than expected in the frontline situation, despite significant TMB and heavy tobacco smoking.1
Reference
- Aldea M, Parisi C, Mogenet A, et al. Molecular features of young cannabis smokers with advanced non-small cell lung cancer (aNSCLC). Ann Oncol. 2021;32(suppl 5):S1024.