Afatinib

Afatinib Reactions 1680, p20 - 2 Dec 2017 Various toxicities: 24 case reports In a retrospective observational study, 24 patients (13 women and 11 men aged 44 82 years) were described, out of which 7 patients developed skin rash, interstitial pneumonitis, oral mucositis or paronychia during treatment with afatinib while the 17 patients developed acquired resistance to afatinib [routes and time to reactions onsets not stated; not all dosages stated]. The patients, who were diagnosed with EGFR mutation- positive lung adenocarcinoma, started receiving treatment with afatinib. Seven out of the 17 patients received afatinib at a dose 40 mg/day for total of 30 353 days and developed treatment-related skin rash (3 patients), interstitial pneumonitis (1 patient), skin rash and oral mucositis (1 patient), oral mucositis (1 patient) and paronychia (1 patient). Remaining 17 patients developed EGFR mutations which included p.L858R and p.T790M (2 patients), p.E709K and p.G719A (1 patient), 19DEL (7 patients), p.L858R (5 patients), p.G719A (1 patient) and 20-INS (1 patient) with MET amplifications detected by fluorescence in situ hybridisation and immunohistochemistry. The development of mutations indicated acquired resistance to afatinib. In seven patients, the treatment with afatinib was discontinued and was switched to gefitinib or erliotinib [outcomes not stated]. Author comment: "Notably, 7 patients (5.0%) discontinued afatinib treatment because of severe side effects. In these patients, despite its clinical effectiveness, afatinib was switched to gefitinib or erlotinib (Supplementary Table 1)." "Seventeen of the 20 rebiopsy specimens were adequate for MET immunohistochemical (IHC) staining (Supplementary Table 4)." "Our findings confirmed that the p.T790M mutation was the main mechanism of acquired resistance, followed by MET amplifications." Liang S-K, et al. Real-world experience of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Oncotarget 8: 90430-90443, No. 52, 26 Jul 2017. Available from: URL: http://doi.org/10.18632/ oncotarget.19563 - Taiwan 803285641 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Afatinib

Reactions Weekly , Volume 1680 (1) – Dec 2, 2017
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Publisher
Springer Journals
Copyright
Copyright © 2017 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-017-38951-4
Publisher site
See Article on Publisher Site

Abstract

Reactions 1680, p20 - 2 Dec 2017 Various toxicities: 24 case reports In a retrospective observational study, 24 patients (13 women and 11 men aged 44 82 years) were described, out of which 7 patients developed skin rash, interstitial pneumonitis, oral mucositis or paronychia during treatment with afatinib while the 17 patients developed acquired resistance to afatinib [routes and time to reactions onsets not stated; not all dosages stated]. The patients, who were diagnosed with EGFR mutation- positive lung adenocarcinoma, started receiving treatment with afatinib. Seven out of the 17 patients received afatinib at a dose 40 mg/day for total of 30 353 days and developed treatment-related skin rash (3 patients), interstitial pneumonitis (1 patient), skin rash and oral mucositis (1 patient), oral mucositis (1 patient) and paronychia (1 patient). Remaining 17 patients developed EGFR mutations which included p.L858R and p.T790M (2 patients), p.E709K and p.G719A (1 patient), 19DEL (7 patients), p.L858R (5 patients), p.G719A (1 patient) and 20-INS (1 patient) with MET amplifications detected by fluorescence in situ hybridisation and immunohistochemistry. The development of mutations indicated acquired resistance to afatinib. In seven patients, the treatment with afatinib was discontinued and was switched to gefitinib or erliotinib [outcomes not stated]. Author comment: "Notably, 7 patients (5.0%) discontinued afatinib treatment because of severe side effects. In these patients, despite its clinical effectiveness, afatinib was switched to gefitinib or erlotinib (Supplementary Table 1)." "Seventeen of the 20 rebiopsy specimens were adequate for MET immunohistochemical (IHC) staining (Supplementary Table 4)." "Our findings confirmed that the p.T790M mutation was the main mechanism of acquired resistance, followed by MET amplifications." Liang S-K, et al. Real-world experience of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Oncotarget 8: 90430-90443, No. 52, 26 Jul 2017. Available from: URL: http://doi.org/10.18632/ oncotarget.19563 - Taiwan 803285641 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680

Journal

Reactions WeeklySpringer Journals

Published: Dec 2, 2017

References

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