Clinicopathological factors vs. molecular model for predicting adjuvant EGFR-TKI benefit in stage I EGFR-mutant non-small cell lung cancer.

Abstract

Background: Adjuvant epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show promising outcomes in early-stage non-small cell lung cancer (NSCLC) with EGFR mutations, but accurately identifying patients who would derive the greatest benefit remains a clinical challenge. We compared the predictive performance of clinicopathological factors and the 14-gene assay to assess postoperative prognosis and predict the potential benefit of adjuvant EGFR-TKIs in stage I NSCLC.

Methods: From March 2013 to February 2019, patients with completely resected stage I NSCLC [8th edition tumor-node-metastasis (TNM) classification staging] and EGFR mutation were included. The 14-gene assay, assessed through quantitative reverse transcription polymerase chain reaction (qPCR), was developed and subsequently validated across diverse international cohorts. Clinicopathological high-risk factors included any feature indicating a higher risk of recurrence based on the National Comprehensive Cancer Network (NCCN) guidelines. The primary endpoint of this study was the 5-year disease-free survival (DFS) rate.

Results: Diagnostic values were evaluated in 180 stage I NSCLC patients. The 14-gene assay demonstrated superior performance compared to clinicopathological factors in predicting recurrence events. Patients with molecular high-risk, rather than clinicopathological high-risk factors, showed a more favorable response to adjuvant EGFR-TKIs. Specifically, adjuvant EGFR-TKIs benefited molecular high-risk patients, regardless of clinicopathological high-risk (DFS rate increased from 65.9% to 95.0%, P=0.02) or low-risk subgroups (80.0% to 100%, P=0.04). Patients with molecular low risk did not show any benefit from EGFR-TKIs, regardless of clinicopathological high-risk (DFS rate increased from 93.3% to 100%, P=0.37) or low-risk subgroups (97.0% to 100%, P=0.73).

Conclusions: The 14-gene assay is proven to be superior to clinicopathological factors, offering valuable guidance for adjuvant EGFR-TKIs decisions in stage I NSCLC.