Post-progression survival in patients with non-small cell lung cancer with clinically acquired resistance to gefitinib

J Korean Med Sci. 2013 Nov;28(11):1595-602. doi: 10.3346/jkms.2013.28.11.1595. Epub 2013 Oct 31.

Abstract

Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (≥ 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.

Keywords: Carcinoma, Non-Small-Cell Lung; Gefitinib; Pemetrexed; Survival.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Gefitinib
  • Glutamates / therapeutic use*
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Pemetrexed
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Survival
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Glutamates
  • Protein Kinase Inhibitors
  • Quinazolines
  • Pemetrexed
  • Guanine
  • Gefitinib