Impact of chronic obstructive pulmonary disease on clinical outcomes of EGFR-mutated non–small cell lung cancer patients receiving osimertinib

Osimertinib is one of the standard treatments for advanced EGFR -mutated non–small cell lung cancer (NSCLC). Although chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis of NSCLC patients, the impact of COPD on clinical outcomes of such patients receiving osimertinib has remained unclear. We retrospectively analyzed 93 patients with EGFR -mutated NSCLC receiving osimertinib as first-line therapy between May 2015 and February 2024. COPD was defined by spirometry as a forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio of <0.7 with a smoking history. Osimertinib efficacy including progression-free survival (PFS) was evaluated according to COPD status. Of the 93 patients, 37 (39.8%) were smokers and 17 (18.3%) had COPD. PFS was significantly shorter in all patients with COPD than in all those without COPD (median, 14.6 versus 21.2 months; P =0.0148), with a similar trend being observed among smokers (median, 14.6 versus 18.8 months; P =0.098). Multivariate analysis adjusted for clinical factors revealed that COPD was independently associated with a shorter PFS (hazard ratio, 2.00 [95% CI, 1.07–3.72]; P =0.029). Adverse events leading to treatment discontinuation (odds ratio [OR], 8.17 [95% CI, 2.23–25.55]; P =0.002) and cardiac events (OR, 6.36 [95% CI, 1.79–20.39]; P =0.007) were more frequent in the COPD group. Coexisting COPD was associated with a shorter PFS for osimertinib and a higher risk of treatment discontinuation, particularly as a result of an increased frequency of cardiac events. Careful cardiac monitoring and optimized management of comorbidities are warranted to improve outcomes.