Molecular Features of Young Cannabis Smokers with Advanced NSCLC

2021 Year in Review - Non–Small-Cell Lung Cancer - Lung Cancer

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

  1. 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.
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