Impact of the epidermal growth factor receptor mutation status on the prognosis of recurrent adenocarcinoma of the lung after curative surgery

BMC Cancer. 2018 Oct 5;18(1):959. doi: 10.1186/s12885-018-4849-9.

Abstract

Background: The prognosis of patients with epidermal growth factor receptor (EGFR) mutant adenocarcinoma of the lung (Mt) and EGFR wild-type adenocarcinoma (Wt) after complete resection of the lung differ; however, the mechanisms responsible for these differences remain unclear. The present study examined the post-operative prognosis of recurrent pulmonary adenocarcinoma patients to evaluate the clinicopathological nature of Mt and contribution of EGFR - tyrosine kinase inhibitors (TKI) to the prognosis of patients.

Methods: The subjects were 237 patients with recurrent pulmonary adenocarcinoma who underwent EGFR mutation analysis, and consisted of 108 patients with recurrent Mt and 129 with recurrent Wt. Multivariate analyses were performed to investigate whether the EGFR status is a prognostic factor for relapse-free survival (RFS) and post-relapse survival (PRS).

Results: RFS was significantly better in Mt than in Wt patients; median RFS were 20.2 and 13.3 months, respectively (p < 0.001). The multivariate analysis identified EGFR mutation as an independent prognostic factor for a favorable RFS (hazard ratio = 0.68; 95% confidence interval, 0.52-0.89). Although, no significant differences were observed in PRS between Mt and Wt patients (median PRS were 33.9 and 28.2 months, respectively; p = 0.360), PRS was significantly better in Mt with EGFR - TKI than in Wt and Mt patients without EGFR - TKI (p = 0.008 and p < 0.001, respectively). PRS was also significantly better in Wt than in Mt patients without EGFR - TKI (p < 0.001). The multivariate analysis identified the administration of EGFR - TKI as an independent prognostic factor for PRS (hazard ratio = 0.60; 95% confidence interval, 0.40-0.89).

Conclusions: EGFR mutation tumors were associated with a significantly better RFS for recurrent pulmonary adenocarcinoma after curative resection of the lung, which represented the less aggressive nature of Mt tumors. However, patients with Mt did not have a favorable prognosis after recurrence unless they received EGFR - TKI.

Keywords: Adenocarcinoma of the lung; Epidermal growth factor receptor mutation; Post-relapse survival; Recurrence; Relapse-free survival; Tyrosine kinase inhibitor.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / surgery*
  • Adult
  • Aged
  • Aged, 80 and over
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies

Substances

  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors