1538O - Environmental pollutants and molecular alterations in non-small cell lung cancer: Insights from the KBP-2020 cohort study

Background

The influence of environmental pollutants on histomolecular alterations in NSCLC, beyond EGFR mutations, remains largely unexplored. We conducted a comprehensive study to elucidate the link between exposure to different pollutants and the presence of key molecular alterations alongside PD-L1 expression in NSCLC.

Methods

The KBP-2020 cohort is a multicenter observational study that included all patients (pts) diagnosed with lung cancer in 2020 at participating centers. Pts with non-squamous NSCLC, known molecular status and known residence were included in this analysis. Average annual exposure over the past 10 years to PM2.5, PM10, NO2, and O3 was collected based on place of residence, and radon exposure risk was segmented into three classes. Results were adjusted for age, sex, pack-year, histologic subtype and stage. They are expressed as odds ratios (OR) with 95% CI.

Results

Of the 8999 pts enrolled in the KBP-2020 cohort, 5778 were included in the present study. The median age was 67 years, 61% were male and 17% were never smokers. KRAS, EGFR, ALK, MET and STK11 alterations were found in 36%, 13%, 2.1%, 5.2% and16% of pts, respectively. PD-L1% expression was <1%, 1-49%, ≥50% in 42%, 31%, 27% of pts, respectively. Median PM2.5 level (3-year lag) was 9.71 mg/m3 [range 6.86-13.05]. Exposure to PM2.5 (3-year lag) was associated with an increased risk of detecting an EGFR mutation with an OR of 1.153 (95%CI 1.051-1.264, p=0.003). A similar association was found for 5 or 10-year lag exposure and for PM10 and NO2. No association was found between PM2.5 exposure and other alterations. However, PM10 exposure was associated with an increased risk of MET and STK11 alterations (OR 1.198, 95%CI 1.062-1.351, p=0.003; OR 1.182, 95%CI 1.075-1.300, p=0.001, respectively). PD-L1 expression was not influenced by exposure to any of the pollutants studied.

Conclusions

These findings underscore the complex interplay between environmental factors and molecular characteristics in NSCLC pathogenesis, highlighting the need for further research to elucidate underlying mechanisms and inform targeted interventions for at-risk populations.

Clinical trial identification

NCT04402099.

Editorial acknowledgement

Legal entity responsible for the study

Collège des Pneumologues des Hôpitaux Généraux.

Funding

AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Chug, Janssen, MSD, Sanofi, Pfizer, Roche, Takeda, Lilly.

Disclosure

A.B. Cortot: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, AstraZeneca, MSD, Pfizer, Novartis, Takeda, Roche; Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer, Janssen, Exeliom, Amgen; Financial Interests, Institutional, Research Grant: Merck, Roche, AbbVie, Exeliom; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: Janssen, Roche, Sparta, Amgen, Mirati, AbbVie; Non-Financial Interests, Member of Board of Directors: French Thoracic Intergroup. D. Debieuvre: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Janssen, Sanofi-Winthrop, Amgen, Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Coordinating PI: Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugaï, Chiesi, Takeda, Bayer, Sanofi-Winthrop, Amgen, AbbVie. All other authors have declared no conflicts of interest.