Real-World Treatment Patterns and Clinical Outcomes in <i>EGFR</i>-Mutant Unresectable Locally Advanced Lung Adenocarcinoma: A Multi-Center Cohort Study

Backgrounds: Chemoradiation therapy (CRT) is the standard care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). The optimal management of patients with epidermal growth factor receptor gene (EGFR) mutant LA-NSCLC is not determine.Methods: We retrospectively collected data from patients with unresectable stage III lung adenocarcinoma (LAC) harboring EGFR mutations from 2012 to 2018 and categorized their primary treatment as CRT (group 1), combined radiation therapy (RT) and EGFR-tyrosine kinase inhibitors (TKI) with/without chemotherapy (group 2), or EGFR-TKI alone until tumor progression (group 3). Inverse probability of multiple treatment weighting (IPTW) of propensity score was used to compare overall survival (OS) and progression free survival (PFS) between treatments and account for confounding.Findings: EGFR mutations were present in 24.1% of genotyped patients (N=516/2137). Of 440 patients with adequate information, 104, 105, and 231 patients were in groups 1-3. Upon IPTW analysis, adjusted median PFS was 12.4, 26.2 and 16.2 months (log-rank P=0.001) for groups 1-3, and median OS was 51.0, 67.4 and 49.3 months (log-rank P= 0.084), respectively. Comparing to CRT, RT+TKI with/without chemotherapy significantly improved both PFS (adjusted HR [aHR], 0.40; 95% CI, 0.29-0.54; P= 0.001) and OS (aHR, 0.61; 95% CI, 0.38-0.98; P=0.039);TKI alone prolonged PFS (aHR=0.66; 95%CI, 0.50-0.87; P=0.003) but not OS (aHR,0.90; 95% CI, 0.62-1.32; P= 0.595). Similar findings were found in doubly robust IPTW analysis and multivariable Cox regression analysis. Interpretation: First-line use of RT+TKI with/without chemotherapy was associated with the longest PFS and OS compared with CRT or TKI alone in patients with EGFR-mutant unresectable LA-NSCLC.Trial Registration: The study was registered with Clinical Trials.gov, number NCT04304638.Funding Statement: This trial was funded by the National Natural Sciences Foundation Key Program (81572971); CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1-005), and Sanming Project of Medicine in Shenzhen (No. SZSM201612063)Declaration of Interests: All authors have declared no conflicts of interest.Ethics Approval Statement: The study protocol was approved by the ethics review boards of the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Each participating center obtained regulatory approval per their institutional ethics guidelines.