Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations

J Thorac Oncol. 2011 Mar;6(3):569-75. doi: 10.1097/JTO.0b013e318202bffe.

Abstract

Background: Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown.

Methods: Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI.

Results: The cohort consists of 167 patients with completely resected stages I to III lung adenocarcinoma. Ninety-three patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, and 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery, and adjuvant platinum chemotherapy, the 2-year disease-free survival (DFS) was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio = 0.53; 95% confidence interval: 0.28-1.03; p = 0.06). The 2-year overall survival was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (hazard ratio: 0.62; 95% confidence interval: 0.26-1.51; p = 0.296).

Conclusions: Compared with patients who did not receive adjuvant TKI, we observed a trend toward improvement in DFS among individuals with resected stages I to III lung adenocarcinomas harboring mutations in EGFR exon 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Combined Modality Therapy
  • DNA, Neoplasm / genetics
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Polymerase Chain Reaction
  • Prospective Studies
  • Quinazolines / administration & dosage
  • Survival Rate
  • Treatment Outcome

Substances

  • DNA, Neoplasm
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib