DGIdb - AFATINIB Drug Record

AFATINIB chembl:CHEMBL1173655 ApprovedAntineoplastic

Alternate Names:

GIOTRIF
AFATINIB
BIBW-2992
GILOTRIF
BIBW2992
AFATINIBUM
GILOTRIF®
BIBW 2992
drugbank:08916
chemidplus:850140-72-6
rxcui:1430438
pubchem.compound:10184653
chembl:CHEMBL1173655

Drug Info:

FDA Approval	not approved
Drug Class	Small molecule
Drug Indications	antineoplastic agent
FDA Approval	Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)
Drug Class	Kinase Inhibitors

(9 More Sources)

Publications:

Liao BC et al., 2015, Second and third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer., Curr Opin Oncol
Yang et al., 2001, Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy., Crit. Rev. Oncol. Hematol.
Rossi A et al., 2013, Should epidermal growth factor receptor tyrosine kinase inhibitors be considered ideal drugs for the treatment of selected advanced non-small cell lung cancer patients?, Cancer Treat Rev
Mayo C et al., 2012, Pharmacogenetics of EGFR in lung cancer: perspectives and clinical applications., Pharmacogenomics
Van Cutsem et al., 2009, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer., N. Engl. J. Med.
Vermorken JB et al., 2008, Platinum-based chemotherapy plus cetuximab in head and neck cancer., N Engl J Med
Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics
Giusti RM et al., 2008, U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens., Clin Cancer Res
Jonker et al., 2007, Cetuximab for the treatment of colorectal cancer., N. Engl. J. Med.
Bonner JA et al., 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck., N Engl J Med
Normanno N et al., 2006, Epidermal growth factor receptor (EGFR) signaling in cancer., Gene
Thatcher N et al., 2005, Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)., Lancet
Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol
Giaccone G et al., 2004, Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1., J Clin Oncol
Jorissen RN et al., 2003, Epidermal growth factor receptor: mechanisms of activation and signalling., Exp Cell Res
Rajasekaran et al., 2010, In silico identification of significant detrimental missense mutations of EGFR and their effect with 4-anilinoquinazoline-based drugs., Appl. Biochem. Biotechnol.
Shi et al., 2013, Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial., Lancet Oncol.
Mitsudomi et al., 2010, Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial., Lancet Oncol.
Rosell et al., 2012, Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial., Lancet Oncol.
Mok et al., 2009, Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma., N. Engl. J. Med.
Sequist et al., 2013, Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations., J. Clin. Oncol.
Fukuoka et al., 2011, Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)., J. Clin. Oncol.
Kosaka et al., 2009, Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma., J Thorac Oncol
Marks et al., 2008, Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma., J Thorac Oncol
Yang et al., 2012, Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial., Lancet Oncol.
Rosell et al., 2009, Screening for epidermal growth factor receptor mutations in lung cancer., N. Engl. J. Med.
Maemondo et al., 2010, Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR., N. Engl. J. Med.
Zhou et al., 2011, Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study., Lancet Oncol.
Miller et al., 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., Lancet Oncol.
Mulloy et al., 2007, Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib., Cancer Res.
Walter et al., 2013, Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC., Cancer Discov
Bell et al., 2005, Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR., Nat. Genet.
Pao et al., 2005, Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain., PLoS Med.
Zhou et al., 2009, Novel mutant-selective EGFR kinase inhibitors against EGFR T790M., Nature
Jänne et al., 2015, AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer., N. Engl. J. Med.
Hirano et al., 2015, In vitro modeling to determine mutation specificity of EGFR tyrosine kinase inhibitors against clinically relevant EGFR mutants in non-small-cell lung cancer., Oncotarget
Ding et al., 2014, The predictive role of pretreatment epidermal growth factor receptor T790M mutation on the progression-free survival of tyrosine-kinase inhibitor-treated non-small cell lung cancer patients: a meta-analysis., Onco Targets Ther
Yun et al., 2008, The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP., Proc. Natl. Acad. Sci. U.S.A.
Inukai et al., 2006, Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer., Cancer Res.
Kobayashi et al., 2005, EGFR mutation and resistance of non-small-cell lung cancer to gefitinib., N. Engl. J. Med.
Wu et al., 2011, Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer., Clin. Cancer Res.
Ai et al., 2014, A systematic profile of clinical inhibitors responsive to EGFR somatic amino acid mutations in lung cancer: implication for the molecular mechanism of drug resistance and sensitivity., Amino Acids
Su et al., 2012, Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer., J. Clin. Oncol.
Katakami et al., 2013, LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both., J. Clin. Oncol.
Girard et al., 2010, Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report., Clin. Cancer Res.
Cross et al., 2014, AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer., Cancer Discov
Sequist et al., 2011, Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors., Sci Transl Med
Oxnard et al., 2012, Screening for germline EGFR T790M mutations through lung cancer genotyping., J Thorac Oncol
Sequist et al., 2016, Osimertinib Responses After Disease Progression in Patients Who Had Been Receiving Rociletinib., JAMA Oncol
Li et al., 2014, Primary concomitant EGFR T790M mutation predicted worse prognosis in non-small cell lung cancer patients., Onco Targets Ther
Denis et al., 2015, EGFR T790M resistance mutation in non small-cell lung carcinoma., Clin. Chim. Acta
Sequist et al., 2015, Rociletinib in EGFR-mutated non-small-cell lung cancer., N. Engl. J. Med.
Watanabe et al., 2011, Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis., BMC Cancer
Li et al., 2014, Response to pemetrexed rechallenge after acquired resistance of EGFR-TKI in a patient with advanced NSCLC., Lung Cancer
Rosell et al., 2011, Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations., Clin. Cancer Res.
Fu et al., 2008, EGFR mutants found in non-small cell lung cancer show different levels of sensitivity to suppression of Src: implications in targeting therapy., Oncogene
Kancha et al., 2009, Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy., Clin. Cancer Res.
Guo et al., 2006, Gefitinib-sensitizing mutations in esophageal carcinoma., N. Engl. J. Med.
Eberhard et al., 2005, Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib., J. Clin. Oncol.
Sequist et al., 2008, First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations., J. Clin. Oncol.
Kobayashi et al., 2013, Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors., J Thorac Oncol
Schick et al., 1990, Effects of marine oil-enriched diets on guinea pig megakaryocyte and platelet lipids: effects on thromboxane synthesis and platelet function., Biochim. Biophys. Acta
Berge et al., 2013, Erlotinib response in an NSCLC patient with a novel compound G719D+L861R mutation in EGFR., J Thorac Oncol
Jiang et al., 2005, Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression., Cancer Res.
Cho et al., 2014, Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab., Mol. Cancer
Greulich et al., 2005, Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants., PLoS Med.
Gilmer et al., 2008, Impact of common epidermal growth factor receptor and HER2 variants on receptor activity and inhibition by lapatinib., Cancer Res.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Ramalingam et al., 2012, Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer., J. Clin. Oncol.
Sequist et al., 2010, Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer., J. Clin. Oncol.
Paez et al., 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy., Science
Pao et al., 2004, EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib., Proc. Natl. Acad. Sci. U.S.A.
Huang et al., 2013, MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib., Mol Oncol
Mitsudomi et al., 2010, Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer., FEBS J.
Lynch et al., 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib., N. Engl. J. Med.
Tam et al., 2009, Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared with common activating missense mutations., Mol. Cancer Ther.
Taron et al., 2005, Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas., Clin. Cancer Res.
Han et al., 2005, Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib., J. Clin. Oncol.
Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.
Rosell et al., 2005, Mutations in the tyrosine kinase domain of the EGFR gene associated with gefitinib response in non-small-cell lung cancer., Lung Cancer
Yang et al., 2015, Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6., Lancet Oncol.
Park et al., 2016, Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial., Lancet Oncol.
Yang et al., 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., Lancet Oncol.
Sun et al., 2013, Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors., Lung Cancer
Belchis et al., 2016, Heterogeneity of resistance mutations detectable by nextgeneration sequencing in TKI-treated lung adenocarcinoma., Oncotarget
Dungo et al., 2013, Afatinib: first global approval., Drugs
Wu et al., 2014, Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial., Lancet Oncol.
Ward RA et al., 2013, Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR)., J Med Chem
Ji X et al., 2014, Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors., Bioorg Med Chem
Bahcall et al., 2016, Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer., Cancer Discov
Konduri et al., 2016, EGFR Fusions as Novel Therapeutic Targets in Lung Cancer., Cancer Discov
Passaro et al., 2013, Afatinib as first-line treatment for patients with advanced non-small-cell lung cancer harboring EGFR mutations: focus on LUX-Lung 3 and LUX-Lung 6 phase III trials., J Thorac Dis
Eberlein et al., 2015, Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models., Cancer Res.
Pirazzoli et al., 2014, Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1., Cell Rep
Smith et al., 2015, The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer., Target Oncol
Pirazzoli et al., 2016, Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma., Clin. Cancer Res.
Krall et al., 2017, KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer., Elife
Wu et al., 2016, The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients., Oncotarget
He et al., 2012, EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma., Clin. Cancer Res.
Khelwatty et al., 2011, Growth response of human colorectal tumour cell lines to treatment with afatinib (BIBW2992), an irreversible erbB family blocker, and its association with expression of HER family members., Int. J. Oncol.
Tsai et al., 2015, Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase Inhibitor Enhances Radiation Effect in Bladder Cancer Cells., Mol. Cancer Ther.
Niederst et al., 2015, The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies., Clin. Cancer Res.
Nakamura et al., 2016, Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC., Mol. Cancer Ther.
Young et al., 2015, Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo., Target Oncol
Choudhury et al., 2016, Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations., J. Clin. Oncol.
Gallant et al., 2015, EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib., Cancer Discov
Kobayashi et al., 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., Clin. Cancer Res.
Yeh et al., 2013, DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy., Clin. Cancer Res.
Yun et al., 2007, Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity., Cancer Cell
Kobayashi et al., 2017, Characterization of EGFR T790M, L792F, and C797S Mutations as Mechanisms of Acquired Resistance to Afatinib in Lung Cancer., Mol. Cancer Ther.
Ercan et al., 2015, EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors., Clin. Cancer Res.
Yasuda et al., 2013, Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer., Sci Transl Med
Kosaka et al., 2017, Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors., Cancer Res.
Heigener et al., 2015, Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors., Oncologist
D'Arcangelo et al., 2014, Clinical and comparative utility of afatinib in non-small cell lung cancer., Biologics
Jensen KV et al., 2020, EGFR blockade in GBM brain tumor stem cells synergizes with JAK2/STAT3 pathway inhibition to abrogate compensatory mechanisms in vitro and in vivo., Neurooncol Adv
Starrett JH et al., 2020, Drug Sensitivity and Allele Specificity of First-Line Osimertinib Resistance <i>EGFR</i> Mutations., Cancer Res
Heining C et al., 2018, <i>NRG1</i> Fusions in <i>KRAS</i> Wild-Type Pancreatic Cancer., Cancer Discov
Jones MR et al., 2019, <i>NRG1</i> Gene Fusions Are Recurrent, Clinically Actionable Gene Rearrangements in <i>KRAS</i> Wild-Type Pancreatic Ductal Adenocarcinoma., Clin Cancer Res
Jones MR et al., 2017, Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer., Ann Oncol
Gay ND et al., 2017, Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions., J Thorac Oncol
Cheema PK et al., 2017, A Case of Invasive Mucinous Pulmonary Adenocarcinoma with a CD74-NRG1 Fusion Protein Targeted with Afatinib., J Thorac Oncol
Chow et al., 2013, Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer., Br. J. Cancer
Lin et al., 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 Res. Treat.
Burstein et al., 2010, Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer., J. Clin. Oncol.
Li et al., 2015, HER2 insertion YVMA mutant lung cancer: Long natural history and response to afatinib., Lung Cancer
Perera et al., 2009, HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy., Proc. Natl. Acad. Sci. U.S.A.
De Grève et al., 2012, Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu., Lung Cancer
Ring et al., 2015, Phase I Study to Assess the Combination of Afatinib with Trastuzumab in Patients with Advanced or Metastatic HER2-Positive Breast Cancer., Clin. Cancer Res.
Cortés et al., 2015, Afatinib alone or afatinib plus vinorelbine versus investigator's choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial., Lancet Oncol.
Goh et al., 2016, Clonal Evolutionary Analysis during HER2 Blockade in HER2-Positive Inflammatory Breast Cancer: A Phase II Open-Label Clinical Trial of Afatinib +/- Vinorelbine., PLoS Med.
Rexer et al., 2013, Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2., Clin. Cancer Res.
de Martino et al., 2014, Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib., Cancer Biol. Ther.
Kavuri et al., 2015, HER2 activating mutations are targets for colorectal cancer treatment., Cancer Discov
Costa et al., 2016, Pulse Afatinib for ERBB2 Exon 20 Insertion-Mutated Lung Adenocarcinomas., J Thorac Oncol
Hanker et al., 2017, An Acquired HER2(T798I) Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer., Cancer Discov
Kwak et al., 2013, Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation., Cancer
Suzawa et al., 2016, Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations., Cancer Sci.
Chuang et al., 2017, ERBB2-Mutated Metastatic Non-Small Cell Lung Cancer: Response and Resistance to Targeted Therapies., J Thorac Oncol
Janjigian et al., 2013, Monitoring afatinib treatment in HER2-positive gastric cancer with 18F-FDG and 89Zr-trastuzumab PET., J. Nucl. Med.
Leto et al., 2015, Sustained Inhibition of HER3 and EGFR Is Necessary to Induce Regression of HER2-Amplified Gastrointestinal Carcinomas., Clin. Cancer Res.
Peters S et al., 2018, Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation-Positive Advanced NSCLC: Findings From a Global Named Patient Use Program., J Thorac Oncol
Sun et al., 2014, Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3., Cell Rep
Manchado et al., 2016, A combinatorial strategy for treating KRAS-mutant lung cancer., Nature
Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.
Tani et al., 2016, Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells., Mol. Cancer Ther.

AFATINIB EGFR

Interaction Score: 4.75

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status NCCN/ CAP guidelines

Clinical Status early trials

Variant Effect gain-of-function

PMIDs:
25611025 11255078 23022519 22594511 19339720 18784101 18681783 18316547 18003960 16467544 16377102 16257339 14990633 14990632 12648464 19455431 23948351 20022809 22285168 19692680 23816960 21670455 19096302 18303429 22452895 19692684 20573926 21783417 22452896 17332364 24065731 16258541 15737014 20033049 25923549 26515464 24623981 18227510 16912157 15728811 21531810 24658966 22215752 23816963 20068085 24893891 21430269 22588155 26720284 24729716 25668228 25923550 21194487 24636847 21233402 17653080 19147750 16707764 16043828 18458038 23242437 2302402 23945392 16204070 24894453 16187797 18199554 25157968 22753918 20479403 15118125 15329413 23102728 19922469 15118073 19671738 16115929 15710947 26619011 16011858 26051236 27083334 25589191 24035188 27304188 23982599 24439929 23930994 24565969 27694386 27102076 23991291 25870145 24813888 25077897 26341921 28145866 26862733 22190593 21617858 25589492 25964297 27207775 25559287 27044931 26286086 26206867 23344264 17349580 27913578 25948633 24353160 28363995 26354527 24790411 32226941 32193290

Sources:
TALC DTC MyCancerGenome TdgClinicalTrial JAX-CKB DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB FDA OncoKB
AFATINIB NRG1

Interaction Score: 1.55

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
29802158 31068372 28950338 28502724 29169524

Sources:
CIViC
AFATINIB ERBB2

Interaction Score: 1.26

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type conflicting

Approval Status Phase I

Indication/Tumor Type Her2-receptor positive breast cancer

PMIDs:
23632474 22418700 20142587 26559459 19122144 22325357 25370464 26596672 27923043 21617858 25589492 23948973 24971884 26243863 26964772 28274957 23775486 27044931 28363995 26545934 28167203 23578997 26296355 30096481

Sources:
TALC MyCancerGenome TdgClinicalTrial JAX-CKB CIViC MyCancerGenomeClinicalTrial
AFATINIB EML4

Interaction Score: 1.24

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Afatinib + Alectinib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
26682573

Sources:
JAX-CKB
AFATINIB ERBB3

Interaction Score: 0.62

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27044931 24685132

Sources:
CIViC
AFATINIB ERBB4

Interaction Score: 0.37

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
27207775

Sources:
JAX-CKB
AFATINIB KRAS

Interaction Score: 0.28

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Afatinib + Cetuximab

Indication/Tumor Type lung adenocarcinoma

Response Type resistant

PMIDs:
25870145 27338794 26341921 24685132

Sources:
JAX-CKB CIViC
AFATINIB NRAS

Interaction Score: 0.26

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB
AFATINIB BRAF

Interaction Score: 0.13

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
26916115

Sources:
JAX-CKB
AFATINIB MET

Interaction Score: 0.12

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Clinical Study

PMIDs:
27694386

Sources:
JAX-CKB

MyCancerGenome: AFATINIB
- Version: 20-Jun-2017
Alternate Names:

BIBW-2992 Development Name

AFATINIB Generic Name

TOMTOVOK Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)

Publications:
TdgClinicalTrial: AFATINIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Publications:

DTC: AFATINIB

Version: 02-September-2020

Alternate Names:

CHEMBL1173655 ChEMBL Drug ID

Drug Info:

Publications:

Ward RA et al., 2013, Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR)., J Med Chem

Ji X et al., 2014, Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors., Bioorg Med Chem

JAX-CKB: Afatinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Tani et al., 2016, Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells., Mol. Cancer Ther.

Waizenegger et al., 2016, A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation., Mol. Cancer Ther.

Choudhury et al., 2016, Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations., J. Clin. Oncol.

DoCM: AFATINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Chang et al., 2016, Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity., Nat. Biotechnol.

Rajasekaran et al., 2010, In silico identification of significant detrimental missense mutations of EGFR and their effect with 4-anilinoquinazoline-based drugs., Appl. Biochem. Biotechnol.

Miller et al., 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., Lancet Oncol.

PharmGKB: afatinib

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Funke S et al., 2008, Pharmacogenetics in colorectal cancer: a systematic review., Pharmacogenomics

Herbst RS et al., 2004, Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2., J Clin Oncol

Bonner JA et al., 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck., N Engl J Med

CIViC: AFATINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Choudhury et al., 2016, Afatinib Activity in Platinum-Refractory Metastatic Urothelial Carcinoma in Patients With ERBB Alterations., J. Clin. Oncol.

Sun et al., 2014, Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer through transcriptional induction of ERBB3., Cell Rep

Perera et al., 2009, HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy., Proc. Natl. Acad. Sci. U.S.A.

TALC: AFATINIB
- Version: 12-May-2016
Alternate Names:

AFATINIB Primary Drug Name

AFATINIB Drug Generic Name

GILOTRIF Drug Trade Name

Drug Info:

Publications:
FDA: Afatinib
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL1173655
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
MyCancerGenomeClinicalTrial: AFATINIB
- Version: 30-February-2014
Alternate Names:

Drug Info:

Publications:
OncoKB: Afatinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
COSMIC: Afatinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Clinical Status	NCCN/ CAP guidelines
Clinical Status	early trials
Variant Effect	gain-of-function

Response Type	conflicting
Approval Status	Phase I
Indication/Tumor Type	Her2-receptor positive breast cancer

combination therapy	Afatinib + Alectinib
Indication/Tumor Type	non-small cell lung carcinoma
Response Type	sensitive

Indication/Tumor Type	head and neck squamous cell carcinoma
Response Type	sensitive
Approval Status	Preclinical - Cell line xenograft

combination therapy	Afatinib + Cetuximab
Indication/Tumor Type	lung adenocarcinoma
Response Type	resistant

Evidence Type	Actionable
Approval Status	Preclinical
Response Type	sensitive

BIBW-2992	Development Name
AFATINIB	Generic Name
TOMTOVOK	Trade Name

AFATINIB	Primary Drug Name
AFATINIB	Drug Generic Name
GILOTRIF	Drug Trade Name

AFATINIB Drug Record

AFATINIB chembl:CHEMBL1173655 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Clinical Status NCCN/ CAP guidelines Clinical Status early trials Variant Effect gain-of-function

Sources: TALC DTC MyCancerGenome TdgClinicalTrial JAX-CKB DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB FDA OncoKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 29802158 31068372 28950338 28502724 29169524

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Response Type conflicting Approval Status Phase I Indication/Tumor Type Her2-receptor positive breast cancer

PMIDs: 23632474 22418700 20142587 26559459 19122144 22325357 25370464 26596672 27923043 21617858 25589492 23948973 24971884 26243863 26964772 28274957 23775486 27044931 28363995 26545934 28167203 23578997 26296355 30096481

Sources: TALC MyCancerGenome TdgClinicalTrial JAX-CKB CIViC MyCancerGenomeClinicalTrial

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Afatinib + Alectinib Indication/Tumor Type non-small cell lung carcinoma Response Type sensitive

PMIDs: 26682573

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27044931 24685132

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Indication/Tumor Type head and neck squamous cell carcinoma Response Type sensitive Approval Status Preclinical - Cell line xenograft

PMIDs: 27207775

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Afatinib + Cetuximab Indication/Tumor Type lung adenocarcinoma Response Type resistant

PMIDs: 25870145 27338794 26341921 24685132

Sources: JAX-CKB CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type non-small cell lung carcinoma Response Type resistant Approval Status Preclinical

PMIDs: 25870145

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Evidence Type Actionable Approval Status Preclinical Response Type sensitive

PMIDs: 26916115

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type lung adenocarcinoma Response Type sensitive Approval Status Clinical Study

PMIDs: 27694386

Sources: JAX-CKB

MyCancerGenome: AFATINIB

Alternate Names: BIBW-2992 Development Name AFATINIB Generic Name TOMTOVOK Trade Name

Drug Info: Drug Class Kinase Inhibitors FDA Approval Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)

Publications:

TdgClinicalTrial: AFATINIB

Alternate Names:

Drug Info: Drug Indications antineoplastic agent Drug Class Small molecule FDA Approval not approved

Publications:

DTC: AFATINIB

Alternate Names: CHEMBL1173655 ChEMBL Drug ID

Drug Info:

JAX-CKB: Afatinib

Alternate Names:

Drug Info:

DoCM: AFATINIB

Alternate Names:

Drug Info:

PharmGKB: afatinib

Alternate Names:

Drug Info:

CIViC: AFATINIB

Alternate Names:

Drug Info:

TALC: AFATINIB

Alternate Names: AFATINIB Primary Drug Name AFATINIB Drug Generic Name GILOTRIF Drug Trade Name

Drug Info:

Publications:

FDA: Afatinib

Alternate Names:

Drug Info:

Publications:

ChemblDrugs: chembl:CHEMBL1173655

Alternate Names:

Drug Info:

Publications:

MyCancerGenomeClinicalTrial: AFATINIB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Clinical Status NCCN/ CAP guidelines

Clinical Status early trials

Variant Effect gain-of-function

Sources:
TALC DTC MyCancerGenome TdgClinicalTrial JAX-CKB DoCM COSMIC CIViC MyCancerGenomeClinicalTrial PharmGKB FDA OncoKB

Interaction Types & Directionality:

n/a

PMIDs:
29802158 31068372 28950338 28502724 29169524

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Response Type conflicting

Approval Status Phase I

Indication/Tumor Type Her2-receptor positive breast cancer

PMIDs:
23632474 22418700 20142587 26559459 19122144 22325357 25370464 26596672 27923043 21617858 25589492 23948973 24971884 26243863 26964772 28274957 23775486 27044931 28363995 26545934 28167203 23578997 26296355 30096481

Sources:
TALC MyCancerGenome TdgClinicalTrial JAX-CKB CIViC MyCancerGenomeClinicalTrial

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Afatinib + Alectinib

Indication/Tumor Type non-small cell lung carcinoma

Response Type sensitive

PMIDs:
26682573

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
27044931 24685132

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Indication/Tumor Type head and neck squamous cell carcinoma

Response Type sensitive

Approval Status Preclinical - Cell line xenograft

PMIDs:
27207775

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Afatinib + Cetuximab

Indication/Tumor Type lung adenocarcinoma

Response Type resistant

PMIDs:
25870145 27338794 26341921 24685132

Sources:
JAX-CKB CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type non-small cell lung carcinoma

Response Type resistant

Approval Status Preclinical

PMIDs:
25870145

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Evidence Type Actionable

Approval Status Preclinical

Response Type sensitive

PMIDs:
26916115

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type lung adenocarcinoma

Response Type sensitive

Approval Status Clinical Study

PMIDs:
27694386

Sources:
JAX-CKB

Alternate Names:

BIBW-2992 Development Name

AFATINIB Generic Name

TOMTOVOK Trade Name

Drug Info:

Drug Class Kinase Inhibitors

FDA Approval Non-small cell lung cancer (with EGFR exon 19 deletions or exon 21 substitution (L858R) mutations)

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Alternate Names:

CHEMBL1173655 ChEMBL Drug ID

Alternate Names:

AFATINIB Primary Drug Name

AFATINIB Drug Generic Name

GILOTRIF Drug Trade Name