First-line Aumolertinib (EGFR tyrosine kinase inhibitor) plus apatinib (VEGFR inhibitor) versus aumolertinib in EGFR-mutant non-small cell lung cancer patients: a randomized, multicenter, phase II trial.

Inactivating vascular endothelial growth factor receptor (VEGFR) may improve the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). The ATTENTION study (phase II, open-label, randomized, multicenter trial (Registration number: ChiCTR2100047453), evaluated the efficacy and safety of aumolertinib plus apatinib vs. aumolertinib alone in untreated, EGFR-mutant, advanced NSCLC. The primary endpoint was the 18-month PFS rate. Across 18 centers in China, 104 patients were enrolled to receive aumolertinib alone (n = 51) or with apatinib (n = 53). At a median follow-up duration of 19.4 months, aumolertinib plus apatinib outperformed aumolertinib alone in terms of the 18-month progression-free survival (PFS) rate (74% vs. 50%, P = 0.036), median PFS (not reached [NR] vs. 20.1 months, hazard ratio [HR] = 0.41, P = 0.017), and objective response rate (79% vs. 59%, P = 0.024). No grade 4/5 treatment-related adverse effects (TRAEs) were observed, whereas grade 3 TRAEs occurred in 38% vs. 27% of patients, with hypertension (11%) and platelet count decrease (9%) being most common in the combination arm. Exploratory analysis revealed that PFS benefits from aumolertinib plus apatinib predominantly in those with TP53 mutations. As an infusion-free option, aumolertinib plus apatinib demonstrated PFS benefits with manageable safety in patients with untreated, EGFR-mutant, advanced NSCLC.