The prognostic implications of EGFR mutation and ALK rearrangement for the long‐term outcomes of patients with resected lung adenocarcinomas

Abstract

Background To investigate the prognostic impact of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement for the overall survival (OS) of patients with surgically treated lung adenocarcinomas. Methods A total of 689 patients with stage I–III lung adenocarcinomas (male:female = 334:355; median age, 64 years) underwent complete surgical resection between 2007 and 2013. The prognostic impact of EGFR mutation and ALK rearrangement on OS was analyzed using Cox regression analysis. Certain clinicopathological prognostic factors (i.e., age, sex, smoking status, nodule type, solid portion size, pathologic stage, adenocarcinoma subtype, and history of adjuvant chemotherapy) were included for adjustments of the hazard ratio (HR). Results EGFR mutation was observed in 438 patients (64%) and ALK rearrangement was seen in 28 patients (4%). Multivariable‐adjusted Cox regression demonstrated that the prognostic effect of EGFR mutation on OS differed by age (HR, exp.[−5.199 + 0.064*age]). The adjusted HR for EGFR mutation was 0.14 (95% CI: 0.05–0.36; P < 0.001) at 50 years, 0.26 (95% CI: 0.15–0.46; P < 0.001) at 60 years, and 0.50 (95% CI: 0.31–0.81; P = 0.005) at 70 years. However, the effect of ALK rearrangement on OS was without statistical significance (P > 0.05). Conclusions EGFR mutation was independently prognostic of the long‐term outcomes of patients with surgically treated lung adenocarcinomas. A more favorable prognostic effect was seen in younger than in older patients. ALK rearrangement was not associated with OS.

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study

“…We found EGFR mutation status to be an independent predictor of OS ( p = 0.004), although post hoc subgroup analyses did not reveal significant differences in survival outcomes with different EGFR mutations, except for an OS benefit observed with Ex19 deletion in stage III disease. Similarly, previous studies and meta-analyses investigating the association of EGFR mutations with survival outcomes in patients with resected NSCLC yielded conflicting results, with some supporting EGFR mutations as a favorable prognostic factor 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 and others reporting either no significant association or association with negative prognosis. 29 , 40 , 41 , 42 The association of EGFR mutations with favorable prognostic factors, including being female and never or light smoking, may influence these observations.…”

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis

“…Patients with BMs also represent those with more advanced disease, and may therefore be more likely to succumb to their disease independent of treatment. In addition, the combination of EGFR and ALK-positive patients in our analysis may have impacted OS results, since the prognosis of patients with these two activating mutations can differ significantly (23,(46)(47)(48)(49).…”

Challenges of neoadjuvant targeted therapy in early stage non-small cell lung cancer—a narrative review

“…A recent Japanese analysis of 244 resected early stage adenocarcinoma, detected EGFR mutations in 44.6% in the whole cohort, while in 50% of 162 patients having pathological stage I disease (27). In a big South Korean series analysis of 689 stage I-III lung adenocarcinomas displayed EGFR mutations in 438 patients (64%) (28).…”