Comparison of Aumolertinib and Gefitinib in First-Line Treatment of EGFR-Mutated NSCLC

Aumolertinib, a novel EGFR inhibitor, shows prolonged clinical benefit in a randomized comparison with gefitinib as first-line therapy in advanced non–small-cell lung cancer (NSCLC) with EGFR exon 19 del or L858R mutation.

Aumolertinib is a novel, irreversible inhibitor of EGFR tyrosine kinase inhibitor (TKI) with favorable pharmacologic properties that selectively inhibits both EGFR sensitizing and resistance mutations. This TKI has been approved in China for the treatment of patients with EGFR-mutated non–small-cell lung cancer (NSCLC) with EGFR T790M who have progressive disease after treatment with an EGFR TKI. The phase 3 trial reported at the American Society of Clinical Oncology 2021 meeting assessed the efficacy and safety of aumolertinib compared with gefitinib as an initial treatment of patients with advanced EGFR-mutated NSCLC.1

Patients with previously untreated metastatic or locally advanced NSCLC and EGFR exon 19 deletion or L858R were randomly assigned in a 1:1 ratio to receive either aumolertinib (110 mg once daily) or gefitinib (250 mg once daily). The primary end point of this study was progression-free survival (PFS) by RECIST version 1.1 per investigator assessment. At 262 PFS events, the study had 90% power to detect a PFS hazard ratio (HR) of 0.67. Secondary end points included overall survival (OS), objective response rate, duration of response (DOR), and safety.1

Between November 30, 2018, and September 6, 2019, 429 patients across 53 sites in China were enrolled and randomized.1 Patient characteristics were well-balanced.1 At the planned final analysis of event-driven PFS, aumolertinib significantly prolonged PFS compared with gefitinib (median PFS, 19.3 vs 9.9 months; HR, 0.46 [95% confidence interval, 0.36-0.60]; P <.0001).1 DOR was also significantly prolonged with aumolertinib.1 Median OS has not been reached.1

Despite a significantly longer duration of treatment (median, 463 vs 254 days) compared with gefitinib, aumolertinib was associated with a lower incidence of rash, diarrhea, aspartate aminotransferase/ alanine aminotransferase increase, and treatment-related serious adverse events (4.2% vs 11.2%).1 Aumolertinib was associated with higher rates of creatine phosphokinase increase, platelet count decrease, and neutrophil count decrease; these toxicities were predominantly low grade in terms of severity.1

Researchers concluded that aumolertinib, a novel EGFR TKI, significantly prolonged PFS and DOR compared with gefitinib as first-line therapy in patients with advanced NSCLC who have an EGFR exon 19 del or L858R mutation. In addition, aumolertinib has a favorable safety profile, especially related to toxicities that are mediated by wild-type EGFR. These results establish aumolertinib as a promising option for these patients.1


1. Lu S, Dong X, Jian H, et al. Randomized phase III trial of aumolertinib (HS-10296, Au) versus gefitinib (G) as first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and EGFR exon 19 del or L858R mutations (EGFRm). Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9013.