Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: Results of an online tumor registry of clinical trials Journal Article

   

Authors:	Jackman, D. M.; Miller, V. A.; Cioffredi, L. A.; Yeap, B. Y.; Jänne, P. A.; Riely, G. J.; Ruiz, M. G.; Giaccone, G.; Sequist, L. V.; Johnson, B. E.
Article Title:	Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: Results of an online tumor registry of clinical trials
Abstract:	Purpose: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR-tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. Experimental Design: Chemotherapy-naïve patients with advanced non-small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. Results: Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of firstline therapy with an EGFR-TKI. Conclusion: EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non-small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib. © 2009 American Association for Cancer Research.
Keywords:	adult; controlled study; human tissue; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; mutation; proto-oncogene proteins; erlotinib; advanced cancer; monotherapy; antineoplastic agents; clinical trials as topic; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; genotype; receptor, epidermal growth factor; drug resistance; protein tyrosine kinase inhibitor; registries; gefitinib; ras proteins; oncogene k ras; quinazolines; databases, factual; drug sensitivity; online systems
Journal Title:	Clinical Cancer Research
Volume:	15
Issue:	16
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2009-08-15
Start Page:	5267
End Page:	5273
Language:	English
DOI:	10.1158/1078-0432.ccr-09-0888
PUBMED:	19671843
PROVIDER:	scopus
PMCID:	PMC3219530
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-69349088824&partnerID=40&md5=4b223bb7b0071045781e271250861cd1
Notes:	--- - "Cited By (since 1996): 37" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus"

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