Initial Patient Characteristics Associated With Ineligibility for Second‐Line Therapy After Progression on First‐Line Osimertinib in EGFR ‐Mutated Non‐Small Cell Lung Cancer

BACKGROUND: Osimertinib, an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), improves survival in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, a substantial proportion of patients do not proceed to subsequent therapy (ST). This study aimed to identify patient characteristics associated with ineligibility for post-osimertinib therapy. METHODS: We retrospectively enrolled patients with EGFR-mutated NSCLC who received first-line osimertinib monotherapy between January 2016 and June 2023. Patients were categorized into a ST group and a non-subsequent therapy (NST) group. Baseline characteristics, treatment outcomes, and reasons for treatment discontinuation were documented. RESULTS: Of 94 patients, 57 (60.6%) received ST, whereas 37 (39.4%) did not. The ST and NST groups significantly differed in age (p < 0.01) and prevalence of baseline central nervous system (CNS) metastases (24.1% vs. 54.1%, p < 0.01). The overall response rate to first-line osimertinib was similar (63.2% vs. 56.8%, p = 0.71), as was median progression-free survival (16.4 [95% confidence interval, CI: 12.4-21.4] vs. 16.1 months [95% CI: 9.8-19.3]; p = 0.24). The primary reason for not receiving subsequent treatment was deterioration in performance status, most often due to worsening pulmonary disease or CNS metastasis. In patients with baseline CNS metastasis, the main cause was also progression of CNS metastasis. CONCLUSIONS: Advanced age and baseline CNS metastasis are significant barriers to receiving second-line therapy after osimertinib monotherapy. Alternate first-line treatment strategies may be warranted for such patients.