The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non-small cell lung cancer with sensitive EGFR mutations

Yu Jiang; Yuechun Lin; Wenhai Fu; Qihua He; Hengrui Liang; Ran Zhong; Ran Cheng; Bingliang Li; Yaokai Wen; Huiting Wang; Jianfu Li; Caichen Li; Shan Xiong; Songan Chen; Jianxing Xiang; Michael J Mann; Jianxing He; Wenhua Liang

doi:10.1016/j.eclinm.2023.102205

The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non-small cell lung cancer with sensitive EGFR mutations

EClinicalMedicine. 2023 Sep 14:64:102205. doi: 10.1016/j.eclinm.2023.102205. eCollection 2023 Oct.

Authors

Yu Jiang^{1

2}, Yuechun Lin^{1

2}, Wenhai Fu^{1

2}, Qihua He^{1

2}, Hengrui Liang^{1

2}, Ran Zhong^{1

2}, Ran Cheng^{1

2}, Bingliang Li³, Yaokai Wen⁴, Huiting Wang^{1

2}, Jianfu Li^{1

2}, Caichen Li^{1

2}, Shan Xiong^{1

2}, Songan Chen⁵, Jianxing Xiang⁵, Michael J Mann⁶, Jianxing He^{1

2}, Wenhua Liang^{1

2}

Affiliations

¹ National Clinical Research Center for Respiratory Disease, Guangzhou, China.
² Departments of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Department of Cardiac Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
⁵ Burning Rock Biotech, Guangzhou, China.
⁶ Department of Surgery, Division of Cardiothoracic Surgery, University of California San Francisco, San Francisco, CA, USA.

Abstract

Background: Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification.

Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics.

Findings: A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR = 0.30, 95% CI, 0.14-0.67; P = 0.003) and OS (HR = 0.26, 95% CI, 0.07-0.96; P = 0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P = 0.007), and IB group (98.8% vs. 75.3%; P = 0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P = 0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P = 0.360).

Interpretation: Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment.

Funding: This work was supported by China National Science Foundation (82022048, 82373121).

Keywords: Adjuvant therapy; EGFR-TKI; Non–small-cell lung cancer; Risk stratification; Stage I.