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Lung Cancer. 2015 Apr;88(1):74-9. doi: 10.1016/j.lungcan.2015.01.026. Epub 2015 Feb 7.

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer.

Author information

1
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama 589-8511, Osaka, Japan.
2
Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp.

Abstract

OBJECTIVES:

Three epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) - afatinib, erlotinib, and gefitinib - are available for the treatment of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Given the long-term exposure of such patients to EGFR-TKIs, the toxicological properties of these agents in these individuals may differ from those observed in unselected patients. We compared the frequencies of severe adverse events (AEs) among EGFR mutation-positive NSCLC patients treated with these three EGFR-TKIs.

MATERIALS AND METHODS:

We performed a pooled analysis of severe AEs according to the type of EGFR-TKI administered with the use of data extracted from prospective clinical trials that evaluated the clinical efficacy of gefitinib, erlotinib, or afatinib in NSCLC patients with EGFR mutations.

RESULTS:

Twenty-one trials published between 2006 and 2014 and including 1468 patients were eligible for analysis. Patients in 13 trials (n=457) received gefitinib, those in 5 trials (n=513) received erlotinib, and those in 3 trials (n=498) received afatinib. Rash and diarrhea of grade ≥3 were significantly more frequent with afatinib therapy than with erlotinib or gefitinib therapy. The frequency of interstitial lung disease (ILD) of grade ≥3 was low (0.6-2.2%) with all three EGFR-TKIs and did not differ significantly among them. Gefitinib was associated with a significantly higher frequency of hepatotoxicity of grade ≥3 compared with erlotinib or afatinib. The overall frequency of AEs leading to treatment withdrawal was 6.1% (83 of 1354 evaluable patients), with such AEs occurring significantly more often with afatinib or gefitinib than with erlotinib. The most common withdrawal AEs were skin toxicity, ILD, and hepatotoxicity.

CONCLUSION:

Such information on AEs should facilitate selection of the most appropriate EGFR-TKI for EGFR mutation-positive NSCLC patients with regard to mitigation of the risk for certain types of toxicity.

KEYWORDS:

Adverse event; Epidermal growth factor receptor; Non-small cell lung cancer; Tyrosine kinase inhibitor; ethnic difference; pooled analysis

PMID:
25704957
DOI:
10.1016/j.lungcan.2015.01.026
[Indexed for MEDLINE]

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