Erlotinib in lung cancer - molecular and clinical predictors of outcome.
BACKGROUND
A clinical trial that compared erlotinib with a placebo for non-small-cell lung cancer demonstrated a survival benefit for erlotinib. We used tumor-biopsy samples from participants in this trial to investigate whether responsiveness to erlotinib and its impact on survival were associated with expression by the tumor of epidermal growth factor receptor (EGFR) and EGFR gene amplification and mutations.


METHODS
EGFR expression was evaluated immunohistochemically in non-small-cell lung cancer specimens from 325 of 731 patients in the trial; 197 samples were analyzed for EGFR mutations; and 221 samples were analyzed for the number of EGFR genes.


RESULTS
In univariate analyses, survival was longer in the erlotinib group than in the placebo group when EGFR was expressed (hazard ratio for death, 0.68; P=0.02) or there was a high number of copies of EGFR (hazard ratio, 0.44; P=0.008). In multivariate analyses, adenocarcinoma (P=0.01), never having smoked (P<0.001), and expression of EGFR (P=0.03) were associated with an objective response. In multivariate analysis, survival after treatment with erlotinib was not influenced by the status of EGFR expression, the number of EGFR copies, or EGFR mutation.


CONCLUSIONS
Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.
Tsao
Ming-Sound
MS
University Health Network, Princess Margaret Hospital Site, and the Ontario Cancer Institute, University of Toronto, Canada.
Sakurada
Akira
A
Cutz
Jean-Claude
JC
Zhu
Chang-Qi
CQ
Kamel-Reid
Suzanne
S
Squire
Jeremy
J
Lorimer
Ian
I
Zhang
Tong
T
Liu
Ni
N
Daneshmand
Manijeh
M
Marrano
Paula
P
da Cunha Santos
Gilda
G
Lagarde
Alain
A
Richardson
Frank
F
Seymour
Lesley
L
Whitehead
Marlo
M
Ding
Keyue
K
Pater
Joseph
J
Shepherd
Frances A
FA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors