Comparative efficacy and safety of almonertinib and osimertinib for advanced non-cellular lung cancer: a real-world non-inferiority study

Abstract

Background Almonertinib is an oral third-generation tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR). It has exhibited substantial antitumor efficacy and well-tolerated toxicity in prior clinical investigations. This study investigated the non-inferiority of almonertinib compared to osimertinib in patients with advanced EGFR-positive non-small cell lung cancer (NSCLC). Method In this retrospective analysis, patients with EGFR-positive NSCLC, experiencing progression after treatment with first- or second-generation EGFR-TKIs were administered either almonertinib or osimertinib, with or without concomitant treatment with anti-angiogenic agents and chemotherapy, until disease progression or the occurrence of unacceptable drug toxicity. Result One hundred eighty-two patients were enrolled in the study and categorized into two groups based on the method of administration: almonertinib (n=79) and osimertinib (n=103). Thirty-nine percent of these patients had central nervous system metastases. Almonertinib exhibited efficacy comparable to that of osimertinib considering progression-free survival (PFS) (HR 0.92, 95% CI 0.65-1.31; median PFS 9.63 months vs. 11.4 months; p=0.65). EGFR-T790M mutations were observed in 75% and 87% of the almonertinib and osimertinib groups, with a median PFS of 15.37 and 12.0 months, respectively, of the two groups (p=0.39). Overall, both groups had manageable safety profile, with the majority being grade 2 and below adverse event. Compared to patients taking osimertinib, those taking almonertinib had fewer drug-related adverse reactions, mainly in terms of subjective patient perception, including onychomycosis, diarrhea, mouth ulcers, and skin rash. Conclusion Almonertinib may be a potentially superior treatment option for patients with advanced NSCLC harboring EGFR mutations, as it demonstrates comparable efficacy to osimertinib while significantly reducing adverse reactions.