Masayuki Takeda1, Isamu Okamoto2, Kazuhiko Nakagawa1. 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.
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 NSCLCpatients 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 NSCLCpatients 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 NSCLCpatients with regard to mitigation of the risk for certain types of toxicity.
Authors: Sanjay Goel; Santiago Viteri; Teresa Morán; Cinthya Coronado; Jorge Luis Iglesias Dios; Bernardo Miguel-Lillo; Eva M Fernández-García; Rafael Rosell Journal: Invest New Drugs Date: 2015-12-02 Impact factor: 3.850
Authors: Giulia Pasello; Giovanni Vicario; Fable Zustovich; Francesco Oniga; Stefania Gori; Francesco Rosetti; Andrea Bonetti; Adolfo Favaretto; Silvia Toso; Roberta Redelotti; Antonio Santo; Daniele Bernardi; Petros Giovanis; Cristina Oliani; Lorenzo Calvetti; Carlo Gatti; Giovanni Palazzolo; Zora Baretta; Alberto Bortolami; Laura Bonanno; Marco Basso; Jessica Menis; Donatella Da Corte; Stefano Frega; Valentina Guarneri; PierFranco Conte Journal: Oncologist Date: 2019-03-07