It has received regulatory approval for use as a treatment for non-small cell lung cancer,[1][5][8][9] although there is emerging evidence to support its use in other cancers such as breast cancer.[10]
Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like erlotinib or gefitinib, but also against less common mutations which are resistant to these drugs. However, it is not active against the T790M mutation which generally requires third generation drugs like osimertinib.[12] Because of its additional activity against Her2, it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers.[3]
In March 2010, a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug.[14] Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival.[15] In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.[16]
In January 2015, a Phase III trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type del 19-positive tumors, compared to cisplatin-based chemotherapy by a year (33 months vs. 21 months).[17] It also shows strong activity against exon 18 mutations (particularly G719) and is currently the preferred EGFR-TKI therapy for exon 18 mutations (particularly G719x).[18][verification needed]
Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib.[10]Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.[19]
^ abcd"Gilotrif (afatinib) tablet, film coated". DailyMed. Boehringer Ingelheim Pharmaceuticals, Inc. 18 October 2019. Retrieved 4 November 2020.
^Spreitzer H (13 May 2008). "Neue Wirkstoffe – Tovok". Österreichische Apothekerzeitung (in German) (10/2008): 498.
^ abMinkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors". Current Opinion in Investigational Drugs. 9 (12): 1336–46. PMID 19037840.
^"Gilotrif (afatinib)" (PDF). US Food and Drug Administration. Retrieved 11 March 2021.
^Vavalà T (2017). "Role of afatinib in the treatment of advanced lung squamous cell carcinoma". Clinical Pharmacology. 9: 147–157. doi:10.2147/CPAA.S112715. PMC5709991. PMID 29225480.
^World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^ ab"Giotrif 20 mg film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Boehringer Ingelheim Limited. 20 January 2014. Retrieved 28 January 2014.
^ ab"Giotrif : EPAR -Product Information" (PDF). European Medicines Agency. Boehringer Ingelheim International GmbH. 16 October 2013. Retrieved 28 January 2014.
^ abLin NU, Winer EP, Wheatley D, Carey LA, Houston S, Mendelson D, et al. (June 2012). "A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab". Breast Cancer Research and Treatment. 133 (3): 1057–65. doi:10.1007/s10549-012-2003-y. PMC3387495. PMID 22418700.
^"Gilotrif (afatinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 28 January 2014.
^Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, et al. (August 2008). "BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models". Oncogene. 27 (34): 4702–11. doi:10.1038/onc.2008.109. PMC2748240. PMID 18408761.
^Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel Frühjahr 2013. (in German)
^Clinical trial number NCT01085136 for "LUX-Lung 5: BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib" at ClinicalTrials.gov
^"Afatinib (BIBW 2992*) Triples Progression Free Survival in Phase III Study in Lung Cancer Patients" (Press release). BusinessWire. 11 October 2010.
^Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, et al. (May 2012). "Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial". The Lancet. Oncology. 13 (5): 528–38. doi:10.1016/S1470-2045(12)70087-6. PMID 22452896.
^Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, et al. (February 2015). "Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials" (PDF). The Lancet. Oncology. 16 (2): 141–51. doi:10.1016/s1470-2045(14)71173-8. PMID 25589191.
^Kobayashi Y, Togashi Y, Yatabe Y, Mizuuchi H, Jangchul P, Kondo C, et al. (December 2015). "EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIs". Clinical Cancer Research. 21 (23): 5305–13. doi:10.1158/1078-0432.CCR-15-1046. PMID 26206867.
^Schuler M, Awada A, Harter P, Canon JL, Possinger K, Schmidt M, et al. (August 2012). "A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer". Breast Cancer Research and Treatment. 134 (3): 1149–59. doi:10.1007/s10549-012-2126-1. PMC3409367. PMID 22763464.
External linksedit
Media related to Afatinib at Wikimedia Commons
"Afatinib". Drug Information Portal. U.S. National Library of Medicine.
"Afatinib dimaleate". Drug Information Portal. U.S. National Library of Medicine.
afatinib, confused, with, apatinib, sold, under, brand, name, gilotrif, among, others, medication, which, used, treat, small, cell, lung, carcinoma, nsclc, belongs, tyrosine, kinase, inhibitor, family, medications, taken, mouth, clinical, datatrade, namesgilot. Not to be confused with apatinib Afatinib sold under the brand name Gilotrif among others is a medication which is used to treat non small cell lung carcinoma NSCLC 2 3 4 It belongs to the tyrosine kinase inhibitor family of medications 5 It is taken by mouth 5 1 AfatinibClinical dataTrade namesGilotrif Giotrif AfanixOther namesBIBW 2992AHFS Drugs comMonographMedlinePlusa613044License dataEU EMA by INN US DailyMed AfatinibPregnancycategoryAU CRoutes ofadministrationBy mouthATC codeL01EB03 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US only 1 EU Rx onlyPharmacokinetic dataProtein binding95 MetabolismCYP not involvedElimination half life37 hoursExcretionFaeces 85 urine 4 IdentifiersIUPAC name N 4 3 Chloro 4 fluorophenyl amino 7 3S tetrahydro 3 furanyl oxy 6 quinazolinyl 4 dimethylamino 2 butenamideCAS Number850140 72 6 Y Drugbank PubChem CID10184653IUPHAR BPS5667DrugBankDB08916 YChemSpider8360155 YUNII41UD74L59MKEGGD09724 Nas salt D09733 NChEBICHEBI 61390 YChEMBLChEMBL1173655 YCompTox Dashboard EPA DTXSID20893451ECHA InfoCard100 239 035Chemical and physical dataFormulaC 24H 25Cl F N 5O 3Molar mass485 94 g mol 13D model JSmol Interactive imageSMILES CN C C C C C O Nc3cc1c Nc cc2Cl ccc2F ncnc1cc3OC4COCC4InChI InChI 1S C24H25ClFN5O3 c1 31 2 8 3 4 23 32 30 21 11 17 20 12 22 21 34 16 7 9 33 13 16 27 14 28 24 17 29 15 5 6 19 26 18 25 10 15 h3 6 10 12 14 16H 7 9 13H2 1 2H3 H 30 32 H 27 28 29 b4 3 t16 m0 s1 YKey ULXXDDBFHOBEHA CWDCEQMOSA N Y N Y what is this verify It is mainly used to treating cases of NSCLC that harbour mutations in the epidermal growth factor receptor EGFR gene 6 It is on the World Health Organization s List of Essential Medicines 7 Contents 1 Medical uses 2 Adverse effects 3 Mechanism of action 4 Clinical trials 5 Society and culture 5 1 Brand names 6 References 7 External linksMedical uses editIt has received regulatory approval for use as a treatment for non small cell lung cancer 1 5 8 9 although there is emerging evidence to support its use in other cancers such as breast cancer 10 Adverse effects editAdverse effects by frequency include 1 5 8 9 11 Very common gt 10 frequency Diarrhea gt 90 Rash dermatitis acneform Stomatitis Paronychia Decreased appetite Nose bleed Itchiness Dry skin Common 1 10 frequency Dehydration Taste changes Dry eye Cystitis Cheilitis Fever Runny stuffy nose Low amount of potassium in the blood Conjunctivitis Increased ALT Increased AST Hand foot syndrome Muscle spasms Kidney impairment and or failure Uncommon 0 1 1 frequency Keratitis Interstitial lung diseaseMechanism of action editLike lapatinib and neratinib afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth factor receptor 2 Her2 and epidermal growth factor receptor EGFR kinases Afatinib is not only active against EGFR mutations targeted by first generation tyrosine kinase inhibitors TKIs like erlotinib or gefitinib but also against less common mutations which are resistant to these drugs However it is not active against the T790M mutation which generally requires third generation drugs like osimertinib 12 Because of its additional activity against Her2 it is being investigated for breast cancer as well as other EGFR and Her2 driven cancers 3 nbsp Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor EGFR via a Michael addition IC50 0 5 nM 13 Clinical trials editIn March 2010 a Phase III trial in NSCLC patients called Lux Lung 5 began with this drug 14 Fall 2010 interim results suggested the drug extended progression free survival threefold compared to placebo but did not extend overall survival 15 In May 2012 the Phase IIb III trial Lux Lung 1 came to the same conclusion 16 In January 2015 a Phase III trial in people with NSCLC suggested the drug extended life expectancy in stage IV NSCLC adenocarcinoma with EGFR Mutation type del 19 positive tumors compared to cisplatin based chemotherapy by a year 33 months vs 21 months 17 It also shows strong activity against exon 18 mutations particularly G719 and is currently the preferred EGFR TKI therapy for exon 18 mutations particularly G719x 18 verification needed Phase II results for breast cancer that over expresses the protein human epidermal growth factor receptor 2 Her2 positive breast cancer were described as promising by the authors with 19 of 41 patients achieving benefit from afatinib 10 Double blind Phase III trials are under way to confirm or refute this finding Her2 negative breast cancers showed limited or no response to the drug 19 Society and culture editBrand names edit This section does not cite any sources Please help improve this section by adding citations to reliable sources Unsourced material may be challenged and removed November 2020 Learn how and when to remove this template message In Bangladesh under the trade name Afanix References edit a b c d Gilotrif afatinib tablet film coated DailyMed Boehringer Ingelheim Pharmaceuticals Inc 18 October 2019 Retrieved 4 November 2020 Spreitzer H 13 May 2008 Neue Wirkstoffe Tovok Osterreichische Apothekerzeitung in German 10 2008 498 a b Minkovsky N Berezov A December 2008 BIBW 2992 a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors Current Opinion in Investigational Drugs 9 12 1336 46 PMID 19037840 Gilotrif afatinib PDF US Food and Drug Administration Retrieved 11 March 2021 a b c d Giotrif Afatinib as afatinib dimaleate PDF TGA eBusiness Services Boehringer Ingelheim Pty Limited 7 November 2013 Retrieved 28 January 2014 Vavala T 2017 Role of afatinib in the treatment of advanced lung squamous cell carcinoma Clinical Pharmacology 9 147 157 doi 10 2147 CPAA S112715 PMC 5709991 PMID 29225480 World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 a b Giotrif 20 mg film coated tablets Summary of Product Characteristics SPC electronic Medicines Compendium Boehringer Ingelheim Limited 20 January 2014 Retrieved 28 January 2014 a b Giotrif EPAR Product Information PDF European Medicines Agency Boehringer Ingelheim International GmbH 16 October 2013 Retrieved 28 January 2014 a b Lin NU Winer EP Wheatley D Carey LA Houston S Mendelson D et al June 2012 A phase II study of afatinib BIBW 2992 an irreversible ErbB family blocker in patients with HER2 positive metastatic breast cancer progressing after trastuzumab Breast Cancer Research and Treatment 133 3 1057 65 doi 10 1007 s10549 012 2003 y PMC 3387495 PMID 22418700 Gilotrif afatinib dosing indications interactions adverse effects and more Medscape Reference WebMD Retrieved 28 January 2014 Li D Ambrogio L Shimamura T Kubo S Takahashi M Chirieac LR et al August 2008 BIBW2992 an irreversible EGFR HER2 inhibitor highly effective in preclinical lung cancer models Oncogene 27 34 4702 11 doi 10 1038 onc 2008 109 PMC 2748240 PMID 18408761 Schubert Zsilavecz M Wurglics M Neue Arzneimittel Fruhjahr 2013 in German Clinical trial number NCT01085136 for LUX Lung 5 BIBW 2992 Plus Weekly Paclitaxel Versus Investigator s Choice of Single Agent Chemotherapy Following BIBW 2992 Monotherapy in Non small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib at ClinicalTrials gov Afatinib BIBW 2992 Triples Progression Free Survival in Phase III Study in Lung Cancer Patients Press release BusinessWire 11 October 2010 Miller VA Hirsh V Cadranel J Chen YM Park K Kim SW et al May 2012 Afatinib versus placebo for patients with advanced metastatic non small cell lung cancer after failure of erlotinib gefitinib or both and one or two lines of chemotherapy LUX Lung 1 a phase 2b 3 randomised trial The Lancet Oncology 13 5 528 38 doi 10 1016 S1470 2045 12 70087 6 PMID 22452896 Yang JC Wu YL Schuler M Sebastian M Popat S Yamamoto N et al February 2015 Afatinib versus cisplatin based chemotherapy for EGFR mutation positive lung adenocarcinoma LUX Lung 3 and LUX Lung 6 analysis of overall survival data from two randomised phase 3 trials PDF The Lancet Oncology 16 2 141 51 doi 10 1016 s1470 2045 14 71173 8 PMID 25589191 Kobayashi Y Togashi Y Yatabe Y Mizuuchi H Jangchul P Kondo C et al December 2015 EGFR Exon 18 Mutations in Lung Cancer Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First or Third Generation TKIs Clinical Cancer Research 21 23 5305 13 doi 10 1158 1078 0432 CCR 15 1046 PMID 26206867 Schuler M Awada A Harter P Canon JL Possinger K Schmidt M et al August 2012 A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2 negative metastatic breast cancer Breast Cancer Research and Treatment 134 3 1149 59 doi 10 1007 s10549 012 2126 1 PMC 3409367 PMID 22763464 External links edit nbsp Media related to Afatinib at Wikimedia Commons Afatinib Drug Information Portal U S National Library of Medicine Afatinib dimaleate Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Afatinib amp oldid 1187672372, wikipedia, wiki, book, books, library,
