{"entity":{"id":"afatinib","kind":"drug","name":"Afatinib","aka":[],"tldr":"Afatinib (Gilotrif) is a second-generation pill that binds EGFR, HER2 and HER4 irreversibly, approved in 2013 for EGFR-mutant lung cancer. Its lasting value is activity against the uncommon EGFR mutations G719X, L861Q and S768I, approved in 2018, because osimertinib has displaced it for common mutations and its wild-type EGFR binding causes more rash and diarrhoea.","summary":"Afatinib is a second-generation, irreversible pan-ErbB tyrosine kinase inhibitor that covalently binds EGFR, HER2 and HER4. LUX-Lung 3 and LUX-Lung 6 (2013) showed superiority over chemotherapy in EGFR-mutant NSCLC, leading to US approval in 2013 for first-line exon 19 deletion or L858R disease, and LUX-Lung 7 compared it with gefitinib. Its distinctive value is activity against uncommon EGFR mutations, G719X, L861Q and S768I, for which it was approved in 2018, and LUX-Lung 8 also supported approval in 2016 for squamous NSCLC after platinum. Because it also hits wild-type EGFR irreversibly, it causes more rash, diarrhoea and paronychia than first-generation agents, and dose reduction is common. Osimertinib has displaced it for common mutations. For a newcomer, afatinib is the EGFR pill to remember for the rarer mutations.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Afatinib","links":[{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=afatinib"}],"tags":["gap-fill"],"related":[],"cancers":["nsclc","egfr-mutant-nsclc","her2-mutant-nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["egfr","her2"],"drugs":[],"companies":["boehringer-ingelheim"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03785249","lux-lung-3"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Afatinib holds a distinct FDA indication, granted in January 2018, for non-resistant uncommon EGFR mutations (S768I, L861Q and G719X), based on a pooled analysis of LUX-Lung 2, 3 and 6. It is the reason a patient with one of those mutations may be offered afatinib rather than osimertinib. There is no NICE appraisal of afatinib for the uncommon mutations."],"brand":"Gilotrif / Giotrif","modality":"Small-molecule pan-ErbB TKI (second generation, irreversible)","mechanism":"Covalent inhibitor of EGFR, HER2 and HER4 kinases.","approvals":[{"region":"US","year":2013,"indication":"First-line metastatic NSCLC with EGFR exon 19 del or L858R"},{"region":"US","year":2016,"indication":"Squamous NSCLC after platinum"},{"region":"US","year":2018,"indication":"Uncommon EGFR mutations (S768I, L861Q, G719X)"},{"region":"EU","year":2013,"indication":"EU brand Giotrif"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/afatinib/","neighbours":{"cancer":[{"id":"chordoma","kind":"cancer","name":"Chordoma","route":"/cancers/chordoma/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"erbb4","kind":"target","name":"HER4 (ERBB4)","route":"/targets/erbb4/"}],"company":[{"id":"boehringer-ingelheim","kind":"company","name":"Boehringer Ingelheim","route":"/companies/boehringer-ingelheim/"}],"trial":[{"id":"nct06486142","kind":"trial","name":"EGFR-mutated Lung Cancer in Randomized Investigator-Initiated Study","route":"/trials/nct06486142/"},{"id":"nct06759857","kind":"trial","name":"FHND9041 Versus Afatinib for Non-small Cell Lung Cancer","route":"/trials/nct06759857/"},{"id":"lux-lung-3","kind":"trial","name":"LUX-Lung 3","route":"/trials/lux-lung-3/"},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/"},{"id":"nct03785249","kind":"trial","name":"Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1","route":"/trials/nct03785249/"},{"id":"nct04183712","kind":"trial","name":"Target Therapy With GEMOX in Recectable Gallbladder Carcinoma Patients Monitored by ctDNA","route":"/trials/nct04183712/"}],"paper":[{"id":"paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","kind":"paper","name":"Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer","route":"/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/"},{"id":"paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019","kind":"paper","name":"Jones 2019: NRG1 gene fusions are recurrent, clinically actionable rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma","route":"/key-papers/paper-jones-nrg1-fusions-recurrent-actionable-kras-wild-type-pdac-ccr-2019/"}],"term":[{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","route":"/terms/egfr-mutation-subtypes/"}],"institution":[{"id":"ntuh","kind":"institution","name":"National Taiwan University Hospital","route":"/institutions/ntuh/"}],"drug":[{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"}],"biomarker":[{"id":"egfr-exon-19-deletion","kind":"biomarker","name":"EGFR exon 19 deletion","route":"/biomarkers/egfr-exon-19-deletion/"},{"id":"egfr-l858r","kind":"biomarker","name":"EGFR L858R","route":"/biomarkers/egfr-l858r/"}]}}