In a Chinese phase III trial (AENEAS2) reported in The Lancet Oncology, Li et al found that the combination of aumolertinib with chemotherapy significantly improved progression-free survival vs aumolertinib alone in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC).
Study Details
In the multicenter open-label trial, 624 patients were randomly assigned between August 2021 and June 2024 to receive aumolertinib at 110 mg once daily (n = 314) or combination therapy (n = 310) with aumolertinib at 110 mg once daily plus pemetrexed at 500 mg/m² with either cisplatin at 75 mg/m² or carboplatin AUC = 5 on day 1 of 21-day cycles for 4 to 6 cycles; patients then received maintenance therapy consisting of aumolertinib once daily or pemetrexed at 500 mg/m² every 3 weeks. The primary endpoint was progression-free survival assessed by blinded independent central review.
Key Findings
Median progression-free survival was 28.9 months (95% confidence interval [CI] = 26.3 months to not reached) in the combination therapy group vs 18.9 months (95% CI = 17.8–21.1 months) in the monotherapy group (hazard ratio [HR] = 0.47, 95% CI = 0.37–0.60, P < .0001).
Adverse events of grade 3 or worse occurred in 80% of the combination group vs 35% of the monotherapy group. The most common grade 3 to 4 adverse events occurring in at least 20% in any group were decreased neutrophil count (55% in the combination group vs 1% in the monotherapy group), decreased white blood cell count (34% vs < 1%), and decreased platelet count (20% vs 1%). Serious adverse events occurred in 36% vs 17% of patients, most commonly hematologic adverse events in the combination group. Adverse events led to dose interruptions in 64% vs 25% of patients, dose reductions in 44% vs 3%, and treatment discontinuation in 21% vs 2% Treatment-related death occurred in one patient in the combination group (due to encephalopathy) and two patients in the monotherapy group (due to pulmonary embolism and respiratory failure).
The investigators concluded: “Aumolertinib in combination with chemotherapy significantly improved progression-free survival. Although this regimen was associated with increased toxicity, the side-effects were managed with dose adjustment and supportive treatment aligned with clinical practice. Long-term follow-up is required to assess overall survival. The AENEAS2 study provides evidence to guide clinical practice regarding EGFR-TKIs and their combination use in treating patients with advanced EGFR-mutated NSCLC.”
Shun Lu, MD, PhD, of Shanghai Lung Cancer Center, Shanghai JiaoTong University, School of Medicine, Shanghai, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Jiangsu Hansoh Pharmaceutical Group and the Collaborative Innovation Center for Clinical and Translational Science by Ministry of Education & Shanghai. For full disclosures of the study authors, visit thelancet.com.
