Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial

Cancer. 2012 Dec 15;118(24):6234-42. doi: 10.1002/cncr.27630. Epub 2012 Jun 6.

Abstract

Background: Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy.

Methods: A phase 3 trial of gefitinib (250 mg/day) versus pemetrexed (500 mg/m(2) on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS).

Results: A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months (P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively (P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively.

Conclusions: Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Glutamates / therapeutic use*
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / therapeutic use
  • Pemetrexed
  • Prognosis
  • Prospective Studies
  • Quinazolines / therapeutic use*
  • Salvage Therapy*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Glutamates
  • Organoplatinum Compounds
  • Quinazolines
  • Pemetrexed
  • Guanine
  • Gefitinib