Efficacy of Almonertinib Versus Osimertinib as the First-Line Treatment for Non-Small Cell Lung Cancer With EGFR L858R Mutation and Prognostic Analysis: A Retrospective Comparative Cohort Study.

OBJECTIVES: Epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors show less efficacy against the EGFR L858R mutation than EGFR 19del, but no current head-to-head clinical trials have been performed comparing the efficacy of almonertinib and osimertinib. Therefore, our study compared the efficacy of these drugs against the EGFR L858R mutation. MATERIALS AND METHODS: A total of 200 patients with non-small cell lung cancer harboring the EGFR L858R mutation were enrolled. Among these patients, 121 received 80 mg of osimertinib, while the other 79 received 110 mg of almonertinib once daily. The primary end point was progression-free survival (PFS). The secondary end points were continued response rate and safety. RESULTS: The median PFS was 18.5 months (95% confidence interval [CI] 16.1-22.5) for osimertinib and 19.4 months (95% CI 13.8-NA) for almonertinib, with a hazard ratio (HR) of 0.92 (95% CI 0.62-1.73), p = 0.69. Forest plots of subgroup analyses showed no significant difference in the median PFS between the almonertinib and osimertinib groups across the subgroups. Osimertinib and almonertinib demonstrated good efficacy in the treatment of patients with brain metastases. The median PFS was 18.6 months (95% CI 15.6-22.8) for patients with brain metastases and 17.1 months (95% CI 14.1-28.6) for those without brain metastases, p = 0.89. Patients with programmed cell death ligand 1 (PD-L1) expression between 1% and 49% and PD-L1 expression < 1% showed no significant differences for their median PFS. The continued response rates between almonertinib and osimertinib were comparable. The differences between almonertinib and osimertinib were minimal. CONCLUSION: Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.