Multicenter phase 3 trial of aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small cell lung cancer

Third-generation EGFR-TKIs are standard first-line therapies for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Their effectiveness is often limited by the emergence of resistance. The phase 3 AENEAS 2 trial, at 60 centers in China, evaluated aumolertinib with or without as first-line treatment for adult patients with locally advanced or metastatic NSCLC with EGFR-sensitive mutations (ex19del/L858R with or without other EGFR mutations). Patients were randomized 1:1 to aulomertinib plus 4 to 6 cycles of pemetrexed plus cisplatin or carboplatin chemotherapy followed by aulomertinib plus pemetrexed maintenance (‘combination therapy’; n=310) or aumolertinib alone (‘monotherapy’; n=314). After median follow-up of 23.4 months, the median BIRC-assessed progression-free survival was 28.9 months with combination therapy versus 18.9 months with monotherapy (HR 0.47; p<0.0001). The most common grade 3-4 adverse events were decrease of neutrophil count (55% in the combination therapy group versus 1% in the monotherapy group), decrease of white blood cell count (34% versus xtagstartz1%), and decrease of platelet count (20% versus 1%); serious adverse events occurred in 36% versus 17%. Treatment-related deaths occurred in one patient in the combination therapy group and two patients in the monotherapy group. The authors conclude that addition of chemotherapy to aulomertinib significantly improved progression-free survival, at the cost of increased toxicity, which was manageable. Long-term follow-up is required to assess overall survival.