Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis.
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), developed for patients with advanced non-small cell lung cancer (NSCLC), give modest results similar to those with chemotherapy. There is evidence of a greater survival benefit from TKIs in patients with certain molecular and clinical features, but results are conflicting. To assess the role of these factors in predicting TKI efficacy, a pooled analysis was performed on data from randomized trials in NSCLC.


METHODS
An electronic search of all randomized trials comparing the efficacy or activity of TKIs and a pooled analysis were performed. The hazard ratio (HR) with 95% confidence interval (CI) was calculated for each level of the factors and an interaction test was used to detect differences in treatment effect related to the different levels.


RESULTS
Of ten randomized trials identified, five were considered for analysis. Smoking was shown to be the only clinical factor to have a predictive effect (non smokers: overall survival (OS) HR 0.53, 95% CI 0.42-0.67; smokers: HR 0.91, 95% CI 0.81-1.02; p-value for interaction <0.001). A negative predictive value was suggested for K-ras mutations (K-ras(+): HR 1.97 95% CI 1.16-3.33; K-ras(-): HR 0.79, 95% CI 0.59-1.05; p-value for interaction 0.003).


CONCLUSIONS
At the present time, none of the biological features which have been evaluated in patients who have undergone therapy using TKIs is proven to be of predictive value; only K-ras mutations and smoking habits can be considered as a possible criteria for selection. Results of prospective randomized trials on biological markers are awaited.
Garassino
Marina Chiara
MC
Oncology Department, Fatebenefratelli and Ophthalmic Hospital, 20121 Milan, Italy. marina.garassino@fbf.milano.it
Borgonovo
Karen
K
Rossi
Antonio
A
Mancuso
Andrea
A
Martelli
Olga
O
Tinazzi
Angelo
A
Di Cosimo
Serena
S
La Verde
Nicla
N
Sburlati
Paola
P
Bianchi
Celso
C
Farina
Gabriella
G
Torri
Valter
V
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors