J Korean Med Sci.  2013 Nov;28(11):1595-1602. 10.3346/jkms.2013.28.11.1595.

Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib

• Kim H
• Yun T
• Lee YJ
• Han JY
• Kim HT
• Lee GK

• KMID: 1777655
• DOI: http://doi.org/10.3346/jkms.2013.28.11.1595

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 (> or = 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.

Keyword

Carcinoma, Non-Small-Cell Lung; Gefitinib; Survival; Pemetrexed

MeSH Terms

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

Figure

• 

  Fig. 1 Algorithm for the identification of patients with advanced non-small cell lung cancer and clinically acquired resistance to gefitinib. NSCLC, non-small cell lung cancer; ECOG PS, ECOG performance status; PFS, progression-free survival; CR, complete response; PR, partial response; SD, stable disease; CNS, central nervous system.

• 

  Fig. 2 Kaplan-Meier curves for survival since progression during gefitinib treatment. (A) Overall, (B) TKI resumed, and (C) pemetrexed administration after gefitinib failure. Survival differences were tested with the log-rank test. TKI, tyrosine kinase inhibitor; OS, overall survival; PD, progressive disease

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