Predictors of outcome for patients with lung adenocarcinoma carrying the epidermal growth factor receptor mutation receiving 1st-line tyrosine kinase inhibitors: Sensitivity and meta-regression analysis of randomized trials

Sara Pilotto; Massimo Di Maio; Umberto Peretti; Stefania Kinspergher; Matteo Brunelli; Francesco Massari; Isabella Sperduti; Diana Giannarelli; Filippo De Marinis; Giampaolo Tortora; Emilio Bria

doi:10.1016/j.critrevonc.2013.11.005

Predictors of outcome for patients with lung adenocarcinoma carrying the epidermal growth factor receptor mutation receiving 1st-line tyrosine kinase inhibitors: Sensitivity and meta-regression analysis of randomized trials

Crit Rev Oncol Hematol. 2014 May;90(2):135-45. doi: 10.1016/j.critrevonc.2013.11.005. Epub 2013 Dec 1.

Affiliations

¹ Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
² Clinical Trials Unit, National Cancer Institute, Napoli, Italy.
³ Department of Pathology and Diagnostic, A.O.U.I., University of Verona, Verona, Italy.
⁴ Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
⁵ Division of Pulmonary Oncology, IEO, Milan, Italy.
⁶ Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy. Electronic address: emiliobria@yahoo.it.

PMID: 24332915
DOI: 10.1016/j.critrevonc.2013.11.005

Abstract

Purpose: We performed a sensitivity and meta-regression analysis, cumulating all randomized trials exploring the benefit of afatinib, erlotinib and gefitinib versus chemotherapy in advanced EGFR mutant NSCLC, to investigate the potential role of additional clinico-pathological predictors of TKIs efficacy.

Results: With regard to progression-free survival (PFS), a significant interaction according to ethnicity (Asian versus Caucasian versus mixed) and to trial design (retrospective versus prospective EGFR analysis), was found; a trend toward significance with regard to type of drug (gefitinib versus erlotinib versus afatinib) was determined. No statistically significant differences in survival were observed. With regard to response, a significant interaction according to ethnicity, trial design and type of drug, was found.

Conclusion: These data, together with a deeper characterization of the molecular background sustaining the oncogenic process, may contribute to create a clinico-pathologic predictive model, aimed to improve the magnitude of benefit expected from the use of targeted agents.

Keywords: Afatinib; Erlotinib; Ethnicity; Gefitinib; Lung cancer; Meta-analysis; Trial design.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenocarcinoma / drug therapy*
ErbB Receptors / genetics*
Humans
Lung Neoplasms / drug therapy*
Mutation*
Protein Kinase Inhibitors / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors*
Randomized Controlled Trials as Topic*
Regression Analysis

Substances

Protein Kinase Inhibitors
ErbB Receptors
Protein-Tyrosine Kinases