Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations Journal Article

Authors: Yeo, W. L.; Riely, G. J.; Yeap, B. Y.; Lau, M. W.; Warner, J. L.; Bodio, K.; Huberman, M. S.; Kris, M. G.; Tenen, D. G.; Pao, W.; Kobayashi, S.; Costa, D. B.
Article Title: Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations
Abstract: PURPOSE: The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) gene mutations. The usual clinical dose of gefitinib (250 mg/d) is only one third of its maximum tolerated dose, whereas the dose of erlotinib (150 mg/d) is at its maximum tolerated dose. In NSCLC cell lines, both TKIs have similar micromolar inhibitory concentrations. We explored whether erlotinib at 25 mg/d (trough serum concentration similar to gefitinib 250 mg/d) would be efficacious in EGFR-mutated NSCLC. METHODS: To study the inhibitory concentrations of gefitinib and erlotinib, we exposed EGFR-mutated cell lines (HCC827, H3255, PC-9, and H1975) to increasing concentrations of these TKIs. Further on, we performed a retrospective evaluation of seven patients with advanced EGFR-mutated (exon 19 deletions and L858R) NSCLC that were given erlotinib at 25 mg/d as their first EGFR TKI. RESULTS: Gefitinib and erlotinib generated similar inhibitory curves across our panel of EGFR-mutated NSCLC cell lines with overlapping mean 50% inhibitory concentration 95% confidence intervals for HCC827, PC-9, and H1975. Both drugs also displayed a high degree of correlation in mean 50% inhibitory concentration (Pearson's r = 0.99, p = 0.0417). Of the seven patients, five patients (71.5%) had partial responses to erlotinib 25 mg/d. Median progression-free survival was 17 months (95% confidence interval, 6-35 months). Toxicities were minimal, with only two (28.5%) patients having a rash and none experiencing (0%) diarrhea. CONCLUSIONS: In NSCLC cell lines, gefitinib and erlotinib have similar inhibitory profiles. In patients with NSCLC and EGFR-activating mutations, a dose of erlotinib 25 mg/d (equivalent to gefitinib 250 mg/d) leads to impressive response rates and progression-free survival similar to the growing experience with the approved doses of gefitinib (250 mg/d) and erlotinib (150 mg/d). Identifying prospectively the lowest and clinically active dose ranges of erlotinib and gefitinib will help further to personalize care for patients with tumors harboring EGFR mutations. © 2010 by the International Association for the Study of Lung Cancer.
Keywords: controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; retrospective studies; gene mutation; human cell; exon; gene deletion; mutation; erlotinib; adenocarcinoma; cell proliferation; progression free survival; lung non small cell cancer; antineoplastic combined chemotherapy protocols; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; lung cancer; receptor, epidermal growth factor; tumor cells, cultured; tyrosine kinase inhibitors; rash; confidence interval; drug response; gefitinib; egfr; quinazolines; non-small cell lung cancer; l858r; exon 19 deletions
Journal Title: Journal of Thoracic Oncology
Volume: 5
Issue: 7
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2010-07-01
Start Page: 1048
End Page: 1053
Language: English
DOI: 10.1097/JTO.0b013e3181dd1386
PUBMED: 20512075
PROVIDER: scopus
PMCID: PMC2893286
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "Source: Scopus"
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MSK Authors
  1. Gregory J Riely
    346 Riely
  2. Mark Kris
    603 Kris