WCLC 2025 - Posters & ePosters-P3.12.44 A Retrospective Study of the Effect of Cumulative Smoking Dose on Clinical Course in People With EGFR-Mutated NSCLC Treated With Osimertinib

P3.12.44 A Retrospective Study of the Effect of Cumulative Smoking Dose on Clinical Course in People With EGFR-Mutated NSCLC Treated With Osimertinib

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This retrospective study from the NHO Kyoto Medical Center evaluated the impact of cumulative smoking dose (CSD) on clinical outcomes in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with the third-generation EGFR tyrosine kinase inhibitor (TKI) osimertinib. The main focus was progression-free survival (PFS) with secondary outcomes including overall survival (OS), objective response rate (ORR), and coexisting genetic mutations.<br /><br />A total of 109 patients were grouped by smoking status: non-smokers (NS, n=64), light smokers (LS, n=20), and heavy smokers (HS, ≥20 pack-years, n=25). Results showed that PFS decreased significantly with increasing CSD. Median PFS was 14.3 months for NS, 9.0 months for LS, and 3.7 months for HS (p=0.031). Cox regression revealed that heavy smoking was associated with a nearly two-fold higher risk of progression (HR 1.93, p=0.010) compared to non-smokers. Although OS was shorter in heavy smokers (24.5 months) compared to non-smokers (30.8 months), this difference was not statistically significant. Disease control rate also declined with increasing CSD (p=0.038), while ORR was similar across groups.<br /><br />The number and types of coexisting genetic mutations did not differ notably among smoking groups. Discussion suggested that smoking-induced genetic alterations likely contribute to poorer PFS by promoting tumor heterogeneity and resistance mechanisms, reducing osimertinib efficacy. Since cytotoxic chemotherapy showed preserved effectiveness irrespective of smoking status in prior studies, combining EGFR-TKIs with chemotherapy may improve outcomes in heavy smokers.<br /><br />Limitations included small sample size, single-center retrospective design, and varied mutation testing methods, limiting generalizability. In conclusion, like first- and second-generation EGFR-TKIs, higher cumulative smoking adversely affects osimertinib efficacy, indicating the need for combination treatment strategies in EGFR-mutated NSCLC patients with significant smoking histories.

Asset Subtitle

Takanori Ito

Meta Tag

Speaker Takanori Ito

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR-mutated NSCLC

osimertinib

cumulative smoking dose

progression-free survival

overall survival

objective response rate

heavy smokers

tyrosine kinase inhibitor

genetic mutations

combination therapy