Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib Journal Article


Authors: Riely, G. J.; Pao, W.; Pham, D.; Li, A. R.; Rizvi, N.; Venkatraman, E. S.; Zakowski, M. F.; Kris, M. G.; Ladanyi, M.; Miller, V. A.
Article Title: Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib
Abstract: Purpose: In patients with non - small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. Experimental Design: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival). Results: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). Conclusions: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations. © 2006 American Association for Cancer Research.
Keywords: adult; cancer survival; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; retrospective studies; gene mutation; major clinical study; exon; gene deletion; mutation; exons; disease course; erlotinib; antineoplastic agents; sensitivity and specificity; polymerase chain reaction; demography; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; genotype; receptor, epidermal growth factor; patient information; gefitinib; dna mutational analysis; point mutation; quinazolines
Journal Title: Clinical Cancer Research
Volume: 12
Issue: 3 I
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2006-02-01
Start Page: 839
End Page: 844
Language: English
DOI: 10.1158/1078-0432.ccr-05-1846
PUBMED: 16467097
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 273" - "Export Date: 4 June 2012" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Allan Rongguo Li
    24 Li
  3. Duykhanh Thi Pham
    13 Pham
  4. William Pao
    141 Pao
  5. Naiyer A Rizvi
    156 Rizvi
  6. Vincent Miller
    259 Miller
  7. Marc Ladanyi
    861 Ladanyi
  8. Gregory J Riely
    344 Riely
  9. Maureen F Zakowski
    275 Zakowski
  10. Mark Kris
    597 Kris