{"entity":{"id":"lapatinib","kind":"drug","name":"Lapatinib","aka":[],"tldr":"Lapatinib was the first HER2-blocking pill (2007) and is now mostly a comparator arm and a late-line option, displaced by tucatinib and ADCs.","summary":"Lapatinib is a reversible, ATP-competitive dual inhibitor of the EGFR and HER2 kinases, and was the first HER2-blocking pill (2007). It is approved with capecitabine for HER2-positive advanced breast cancer after trastuzumab (EGF100151: time to progression 8.4 versus 4.4 months) and with letrozole in hormone receptor-positive, HER2-positive disease. The adjuvant ALTTO trial was negative and neoadjuvant NeoALTTO raised pathological complete response but not survival, so it never established a role in early disease. Diarrhoea and rash are the main toxicities, with a hepatotoxicity warning. It has been displaced by tucatinib and by antibody-drug conjugates and now serves mainly as the control arm in ACE-Breast-02 and other Chinese ADC trials. For a newcomer, lapatinib is the original HER2 pill, now mostly a comparator and a late-line option.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Lapatinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lapatinib"}],"tags":[],"related":[],"cancers":["breast-her2-positive","her2-positive-breast-brain-metastases","colorectal"],"sections":[],"technologies":["kinase-inhibitors","her2-tyrosine-kinase-inhibitors"],"targets":["her2","egfr"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["ace-breast-02","nct06313983"],"people":[],"bottlenecks":[],"keyPapers":["paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"brand":"Tykerb","modality":"Small-molecule reversible HER2/EGFR kinase inhibitor","mechanism":"Reversible dual EGFR/HER2 ATP-competitive inhibitor.","approvals":[{"region":"US","year":2007,"indication":"HER2+ advanced breast cancer with capecitabine after trastuzumab"},{"region":"US","year":2010,"indication":"HR+/HER2+ metastatic breast cancer with letrozole"}],"mechanismSteps":[],"dosing":{"route":"Oral","schedule":"1250 mg once daily with capecitabine; 1500 mg with letrozole","monitoring":"Liver function, LVEF"},"toxicity":[{"event":"Diarrhoea","anyGradePct":65,"grade3PlusPct":13},{"event":"Palmar-plantar erythrodysaesthesia (with capecitabine)","anyGradePct":53},{"event":"Rash","anyGradePct":28}],"access":[],"regulatoryEvents":[{"date":"2010-01-29","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"In combination with letrozole for post-menopausal women with HR-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated"},{"date":"2018-12-06","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2010 converted to traditional approval 8.9 years after it was granted.","indication":"In combination with letrozole for post-menopausal women with HR-positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated"}]},"route":"/drugs/lapatinib/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"}],"technology":[{"id":"her2-tyrosine-kinase-inhibitors","kind":"technology","name":"HER2 tyrosine kinase inhibitors","route":"/technologies/her2-tyrosine-kinase-inhibitors/"},{"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/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"trial":[{"id":"nct06313983","kind":"trial","name":"A Phase Ⅲ Study of Hemay022 in Combination With AI In Advanced Breast Cancer","route":"/trials/nct06313983/"},{"id":"ace-breast-02","kind":"trial","name":"ACE-Breast-02","route":"/trials/ace-breast-02/"},{"id":"geparsixto","kind":"trial","name":"GeparSixto","route":"/trials/geparsixto/"},{"id":"heracles","kind":"trial","name":"HERACLES","route":"/trials/heracles/"},{"id":"nct03784014","kind":"trial","name":"Molecular Profiling of Advanced Soft-tissue Sarcomas","route":"/trials/nct03784014/"},{"id":"nala","kind":"trial","name":"NALA","route":"/trials/nala/"},{"id":"nct03262935","kind":"trial","name":"SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer","route":"/trials/nct03262935/"}],"paper":[{"id":"paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","kind":"paper","name":"A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","route":"/key-papers/paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011/"},{"id":"paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016","kind":"paper","name":"Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES)","route":"/key-papers/paper-sartore-bianchi-heracles-trastuzumab-lapatinib-lancet-oncol-2016/"}],"person":[{"id":"thomas-bachelot","kind":"person","name":"Thomas Bachelot","route":"/people/thomas-bachelot/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"}]}}