Improved survival in patients with unresectable stage III EGFR-mutant adenocarcinoma with upfront EGFR-tyrosine kinase inhibitors

Abstract

Background: Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been the standard treatment for advanced EGFR-mutant adenocarcinoma, the effects of upfront EGFR-TKI use in unresectable stage III EGFR-mutant adenocarcinoma remain unexplored. Here, we conducted a retrospective study to compare different treatment strategies in these patients.

Methods: From October 2010 to June 2019, patients with unresectable stage III adenocarcinoma who received treatment at a tertiary referral center were enrolled. Patients were classified into three groups: EGFR-mutant adenocarcinoma treated with concurrent chemoradiotherapy (group 1) or EGFR-TKI (group 2) and EGFR wild-type adenocarcinoma treated with concurrent chemoradiotherapy (group 3). Progression-free survival, progression-free survival-2, and overall survival were estimated and compared using Kaplan-Meier and log-rank tests.

Results: A total of 92 patients were enrolled; 10, 40, and 42 patients were assigned to groups 1, 2, and 3, respectively. Patients with EGFR mutations who received upfront EGFR-TKIs had significantly longer progression-free and overall survival than those who received upfront concurrent chemoradiotherapy (hazard ratio 0.33 vs. 0.34, p = 0.006 vs. 0.031) according to a Cox model adjusted for possible confounders. Moreover, upfront concurrent chemoradiotherapy did not lead to higher survival rates in patients with EGFR mutations than in those with EGFR wild-type adenocarcinoma (progression-free survival; hazard ratio 0.37, p = 0.036; overall survival; hazard ratio 0.35, p = 0.080) by Cox regression analysis.

Conclusion: This current study suggests that EGFR-TKIs is a better choice for patients with unresectable stage III EGFR-mutant adenocarcinoma. However, further randomized studies are required to validate the results.

Keywords: adenocarcinoma; chemoradiotherapy; epidermal growth factor receptor; stage III; tyrosine kinase inhibitors.

FIGURE 1

Study flowchart

FIGURE 2

(a) PFS, (b) PFS2, and (c) OS among patients with EGFR‐mutant adenocarcinoma receiving CCRT (Group 1) or upfront EGFR‐TKI (Group 2), and patients with EGFR wild‐type adenocarcinoma receiving CCRT (Group 3). CCRT, concurrent chemoradiotherapy; EGFR, epidermal growth factor receptor; PFS, progression‐free survival; OS, overall survival; EGFR‐TKI, epidermal growth factor receptor‐tyrosine kinase inhibitor; PFS2, progression‐free survival‐2