Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis.
Ann Oncol
; 22(10): 2277-85, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21325444
ABSTRACT
BACKGROUND:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are effective as first-line treatment of advanced non-small-cell lung cancer patients with EGFR mutations (EGFR-M+). PATIENTS ANDMETHODS:
We conducted a literature-based meta-analysis to quantify the magnitude of benefit with upfront EGFR TKI in EGFR-M+ patients. Meta-regression and sensitivity analyses were also carried out to identify additional predictors of outcome and to assess the influence of trial design.RESULTS:
Five trials (805 patients) were identified (three trials prospectively enrolling EGFR-M+ patients and two retrospective analyses of EGFR-M+ patients). TKI significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.45, 95% confidence interval (CI) 0.36-0.58, P < 0.0001] and overall response rate (ORR) (HR 2.08, 95% CI 1.75-2.46, P < 0.0001)] over chemotherapy, while significantly decreasing neutropenia. No significant difference was observed in overall survival. The rate of exon-19 mutations, female gender, and nonsmoking status were identified as additional predictors of outcome at meta-regression analysis. A significant interaction with trial design was found for both PFS (P = 0.028) and ORR (P = 0.008), suggesting a larger advantage for patients treated within prospective trials.CONCLUSIONS:
In EGFR-M+ patients, first-line TKI increase both PFS and ORR by ~25%, while significantly decreasing toxicity. The role of additional predictive factors and the influence of trial design on the magnitude of the observed benefit warrant further investigation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Inibidores de Proteínas Quinases
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Receptores ErbB
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Neoplasias Pulmonares
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Mutação
Tipo de estudo:
Clinical_trials
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Prognostic_studies
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Systematic_reviews
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article