# 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

**Authors:** Fan Zhang, Zhendong Zheng, Hongmei Zhang, Xiaolong Yan, Zhefeng Liu, Fan Yang, Juyi Wen, Xin Gan, Lin Wu, Shundong Cang, Hongmei Wang, Jun Zhao, Liang Peng, Xiaosong Li, Zaiwen Fan, Ge Shen, Qiong Zhou, Jinjing Zou, Yu Xu, Lei Zhang, Mingfang Zhao, Shangli Cai, Yi Hu

PMC · DOI: 10.1038/s41392-025-02550-y · Signal Transduction and Targeted Therapy · 2026-02-02

## TL;DR

Combining aumolertinib and apatinib improves survival and response rates in EGFR-mutant lung cancer patients compared to aumolertinib alone.

## Contribution

A new combination therapy for EGFR-mutant NSCLC shows improved progression-free survival and response rates.

## Key findings

- The combination of aumolertinib and apatinib improved 18-month PFS rate to 74% compared to 50% with aumolertinib alone.
- Median PFS was not reached in the combination group versus 20.1 months with aumolertinib alone.
- The combination therapy showed a higher objective response rate (79% vs. 59%).

## Abstract

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.

## Linked entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956], TP53 (tumor protein p53) [NCBI Gene 7157]
- **Chemicals:** aumolertinib (PubChem CID 121280087), apatinib (PubChem CID 45139106)
- **Diseases:** non-small cell lung cancer (MONDO:0005233)

## Full-text entities

- **Genes:** GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, LOC102724197 (inactive glutathione hydrolase 2) [NCBI Gene 102724197] {aka GGT2}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}
- **Diseases:** adenocarcinoma (MESH:D000230), ATTENTION (MESH:D001289), stage IIIB-IV (MESH:C566890), cytotoxic (MESH:D064420), Solid Tumors (MESH:D009369), pressure ulcers (MESH:D003668), proteinuria (MESH:D011507), Lung cancer (MESH:D008175), brain metastases (MESH:D001932), NSCLC (MESH:D002289), hypertension (MESH:D006973), rash (MESH:D005076), pneumonia (MESH:D011014), diarrhea (MESH:D003967), pleural effusion (MESH:D010996), PD (MESH:D010300), stage IV disease (MESH:D007676), death (MESH:D003643), TRAEs (MESH:D016609), central nervous system (CNS) metastasis (MESH:D009362), COVID-19 (MESH:D000086382)
- **Chemicals:** amivantamab (MESH:C000718215), Apatinib (MESH:C553458), TEAE (-), Aumolertinib (MESH:C000718108), platinum (MESH:D010984), erlotinib (MESH:D000069347), ramucirumab (MESH:C543333), bevacizumab (MESH:D000068258), pemetrexed (MESH:D000068437), gefitinib (MESH:D000077156), osimertinib (MESH:C000596361)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** T790M, L861Q, G719A, L858R, G719C

## Full text

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## Figures

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## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12864929/full.md

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Source: https://tomesphere.com/paper/PMC12864929