Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: a randomized, phase II study

Ann Surg Oncol. 2014 Jun;21(6):2091-6. doi: 10.1245/s10434-014-3586-9. Epub 2014 Mar 1.

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown.

Methods: In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS).

Results: From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated.

Conclusions: The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Pemetrexed
  • Pneumonectomy
  • Prospective Studies
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Survival Rate

Substances

  • Glutamates
  • Quinazolines
  • Pemetrexed
  • Guanine
  • Carboplatin
  • ErbB Receptors
  • Gefitinib