In a Chinese phase III trial (AENEAS) reported in the Journal of Clinical Oncology, Lu et al found that aumolertinib, a third-generation EGFR tyrosine kinase inhibitor approved in China, significantly improved progression-free survival vs gefitinib in the first-line treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation.
Study Details
In the double-blind, multicenter trial, 429 patients were randomly assigned between November 2018 and September 2019 to receive aumolertinib at 110 mg once daily (n = 214) or gefitinib at 250 mg once daily (n = 215). The primary endpoint was investigator-assessed progression-free survival.
Progression-Free Survival
Median follow-up was 20.5 months in the aumolertinib group and 20.7 months in the gefitinib group. Median progression-free survival was 19.3 months (95% confidence interval [CI] = 17.8–20.8 months) in the aumolertinib group vs 9.9 months (95% CI = 8.3–12.6 months) in the gefitinib group (hazard ratio [HR] = 0.46, 95% CI = 0.36–0.60, P < .0001). Rates at 1 and 2 years were 69.5% vs 46.3% and 32.5% vs 12.9%.
Objective response was achieved in 73.8% vs 72.1% of patients (P = .6939; complete response in 1 patient in each group), with median response durations of 18.1 months vs 8.3 months (HR = 0.38, P < .0001). Disease control rates were 93.0% vs 96.7% (P = .0884). Overall survival data at the time of analysis showed that death had occurred in 54 vs 69 patients; 12-month rates were 86.2% vs 85.3%.
KEY POINTS
- Aumolertinib significantly improved progression-free survival vs gefitinib.
- Median progression-free survival was 19.3 vs 9.9 months.
Adverse Events
The most common adverse events of any grade in the aumolertinib and gefitinib groups were blood creatine phosphokinase increase (35.5% vs 9.3%), aspartate transaminase increase (29.9% vs 54.0%), alanine transaminase increase (29.4% vs 55.8%), rash (23.4% vs 41.4%), and diarrhea (16.4% vs 35.8%). Grade ≥ 3 adverse events occurred in 36.4% vs 35.8% of patients. Serious adverse events occurred in 22.0% vs 21.4%. Adverse events led to treatment discontinuation in 3.7% vs 5.1%. Adverse events led to death in five patients in the aumolertinib group and three patients in the gefitinib group; relationship to treatment could not be determined in one patient in each group, with all other deaths considered unrelated to treatment.
The investigators concluded, “Aumolertinib is a well-tolerated third-generation EGFR tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.”
Shun Lu, MD, of the Department of Medical Oncology, Shanghai Chest Hospital, Shanghai JiaoTong University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Hansoh Pharmaceutical Group Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
