PMID- 19671843
OWN - NLM
STAT- MEDLINE
DCOM- 20091229
LR  - 20220416
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 16
DP  - 2009 Aug 15
TI  - 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.
PG  - 5267-73
LID - 10.1158/1078-0432.CCR-09-0888 [doi]
AB  - 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-naive 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 first-line 
      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.
FAU - Jackman, David M
AU  - Jackman DM
AD  - Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA. djackman@partners.org
FAU - Miller, Vincent A
AU  - Miller VA
FAU - Cioffredi, Leigh-Anne
AU  - Cioffredi LA
FAU - Yeap, Beow Y
AU  - Yeap BY
FAU - Janne, Pasi A
AU  - Janne PA
FAU - Riely, Gregory J
AU  - Riely GJ
FAU - Ruiz, Marielle Gallegos
AU  - Ruiz MG
FAU - Giaccone, Giuseppe
AU  - Giaccone G
FAU - Sequist, Lecia V
AU  - Sequist LV
FAU - Johnson, Bruce E
AU  - Johnson BE
LA  - eng
GR  - R01 CA114465/CA/NCI NIH HHS/United States
GR  - R01 CA114465-05/CA/NCI NIH HHS/United States
GR  - 5R01 CA 114465-05/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090811
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*diagnosis/drug therapy/genetics
MH  - *Clinical Trials as Topic/classification
MH  - Databases, Factual
MH  - ErbB Receptors/antagonists & inhibitors/*genetics/physiology
MH  - Erlotinib Hydrochloride
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/*diagnosis/drug therapy/genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/physiology
MH  - Online Systems
MH  - Prognosis
MH  - Proto-Oncogene Proteins/*genetics/physiology
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quinazolines/therapeutic use
MH  - *Registries
MH  - ras Proteins/*genetics/physiology
PMC - PMC3219530
MID - NIHMS335809
COIS- Disclosure of Potential Conflicts of Interest D.M. Jackman, consultant, 
      Genentech; honoraria, Roche. V.A. Miller, consultant, Genentech. P.A. Janne, 
      consultant, AVEO Pharmaceuticals, Boehringer Ingelheim, Roche; research funding, 
      Pfizer, Genentech; patent holder, Genzyme. G.J. Riely, consultant, Astra Zeneca, 
      Roche. M.I. Gallegos Ruiz, employment, Roche. B.E. Johnson, consultant, patent 
      holder, Genzyme. The other authors report no conflicts of interest.
EDAT- 2009/08/13 09:00
MHDA- 2009/12/30 06:00
PMCR- 2011/11/17
CRDT- 2009/08/13 09:00
PHST- 2009/08/13 09:00 [entrez]
PHST- 2009/08/13 09:00 [pubmed]
PHST- 2009/12/30 06:00 [medline]
PHST- 2011/11/17 00:00 [pmc-release]
AID - 1078-0432.CCR-09-0888 [pii]
AID - 10.1158/1078-0432.CCR-09-0888 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Aug 15;15(16):5267-73. doi: 10.1158/1078-0432.CCR-09-0888. 
      Epub 2009 Aug 11.