Is there evidence for different effects among EGFR-TKIs? Systematic review and meta-analysis of EGFR tyrosine kinase inhibitors (TKIs) versus chemotherapy as first-line treatment for patients harboring EGFR mutations

Eva Regina Haspinger; Francesco Agustoni; Valter Torri; Francesco Gelsomino; Marco Platania; Nicoletta Zilembo; Rosaria Gallucci; Marina Chiara Garassino; Michela Cinquini

doi:10.1016/j.critrevonc.2014.11.005

Is there evidence for different effects among EGFR-TKIs? Systematic review and meta-analysis of EGFR tyrosine kinase inhibitors (TKIs) versus chemotherapy as first-line treatment for patients harboring EGFR mutations

Crit Rev Oncol Hematol. 2015 May;94(2):213-27. doi: 10.1016/j.critrevonc.2014.11.005. Epub 2014 Nov 22.

Authors

Eva Regina Haspinger¹, Francesco Agustoni¹, Valter Torri², Francesco Gelsomino¹, Marco Platania¹, Nicoletta Zilembo¹, Rosaria Gallucci¹, Marina Chiara Garassino³, Michela Cinquini²

Affiliations

¹ Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
² Fondazione IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
³ Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: marina.garassino@istitutotumori.mi.it.

PMID: 25523487
DOI: 10.1016/j.critrevonc.2014.11.005

Abstract

Three EGFR tyrosine kinase inhibitors have been compared to standard chemotherapy as up-front treatment in patients with advanced EGFR-positive NSCLC. We performed a systematic review and meta-analysis using indirect comparisons to estimate the risk/benefit associated with each drug. EGFR-TKIs fared better than chemotherapy in terms of PFS. The relative probability of overall response was gefitinib versus erlotinib 0.96 (95% CI 0.69-1.34), gefitinib versus afatinib 0.91 (95% CI 0.67-1.23), erlotinib versus afatinib 0.94 (95% CI 0.65-1.35). Indirect comparisons for safety showed the RR for diarrhea gefitinib versus erlotinib 0.80 (95% CI 0.63-1.01), gefitinib versus afatinib 0.29 (95% CI 0.20-0.41), erlotinib versus afatinib 0.36 (95% CI 0.25-0.54); for rash gefitinib versus erlotinib 1.00 (95% CI 0.82-1.22), gefitinib versus afatinib 0.41(95% CI 0.25-0.65), erlotinib versus afatinib 0.41 (95% CI 0.25-0.66); for hypertransaminasemia gefitinib versus erlotinib 2.29 (95% CI 1.63-3.23). Our analysis showed that all treatments had similar efficacy but they differ for toxicities.

Keywords: EGFR-TKI; First line; NSCLC; Review.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Clinical Trials as Topic
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics*
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics*
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Mutation*
Odds Ratio
Proportional Hazards Models
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / therapeutic use*
Treatment Outcome

Substances

Protein Kinase Inhibitors
ErbB Receptors