{"entity":{"id":"alpelisib","kind":"drug","name":"Alpelisib","aka":[],"tldr":"Alpelisib was the first PI3K drug for PIK3CA-mutant breast cancer (2019). It is effective, but high blood sugar and rash limited its use, and newer drugs are displacing it.","summary":"SOLAR-1: PFS 11.0 vs 5.7 months with fulvestrant in PIK3CA-mutant disease. Hyperglycaemia (grade 3-4 ~37%), rash, and diarrhoea are frequent; requires metformin prophylaxis strategies. Superseded in first-line endocrine-resistant disease by inavolisib and in the unselected AKT-pathway-altered population by capivasertib.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Alpelisib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Alpelisib"}],"tags":[],"related":["er-status","pik3ca-hotspot-mutation"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"targets":["pik3ca"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":["hyperglycaemia"],"trials":["solar-1","nct05501886","nct04208178","nct05948943","nct05563220","nct05646862","nct05230810","nct05038735","nct04524000","nct04544189"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Piqray","modality":"Small-molecule PI3Kα inhibitor","mechanism":"ATP-competitive PI3Kα-selective inhibitor.","approvals":[{"region":"US","year":2019,"indication":"PIK3CA-mutant HR+/HER2- advanced breast cancer with fulvestrant after endocrine therapy"}],"mechanismSteps":[],"dosing":{"route":"Oral","schedule":"300 mg once daily with fulvestrant","modifications":"Reduce to 250 then 200 mg for hyperglycaemia/rash","monitoring":"Fasting glucose and HbA1c before and during; antihistamine prophylaxis for rash"},"toxicity":[{"event":"Hyperglycaemia","anyGradePct":64,"grade3PlusPct":37},{"event":"Diarrhoea","anyGradePct":58,"grade3PlusPct":7},{"event":"Rash","anyGradePct":36,"grade3PlusPct":10}],"access":[],"regulatoryEvents":[{"date":"2022-04-05","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 4.5 years later, when the FDA's table was read.","indication":"Treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy"},{"date":"2024-04-24","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.4 years later, when the FDA's table was read.","indication":"Formulation: Treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy."}]},"route":"/drugs/alpelisib/","neighbours":{"biomarker":[{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"technology":[{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"chemical-carcinogenesis-receptor-activation","kind":"pathway","name":"Chemical carcinogenesis - receptor activation","route":"/pathways/chemical-carcinogenesis-receptor-activation/"},{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","route":"/pathways/choline-metabolism-in-cancer/"},{"id":"micrornas-in-cancer","kind":"pathway","name":"MicroRNAs in cancer","route":"/pathways/micrornas-in-cancer/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"term":[{"id":"hyperglycaemia","kind":"term","name":"Hyperglycaemia (PI3K/AKT inhibitor class effect)","route":"/terms/hyperglycaemia/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"}],"trial":[{"id":"nct05646862","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy","route":"/trials/nct05646862/"},{"id":"nct05948943","kind":"trial","name":"Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.","route":"/trials/nct05948943/"},{"id":"nct05230810","kind":"trial","name":"Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.","route":"/trials/nct05230810/"},{"id":"nct05501886","kind":"trial","name":"Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)","route":"/trials/nct05501886/"},{"id":"nct05563220","kind":"trial","name":"Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer","route":"/trials/nct05563220/"},{"id":"solar-1","kind":"trial","name":"SOLAR-1","route":"/trials/solar-1/"},{"id":"nct04524000","kind":"trial","name":"Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer","route":"/trials/nct04524000/"},{"id":"nct04544189","kind":"trial","name":"Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer","route":"/trials/nct04544189/"},{"id":"nct04208178","kind":"trial","name":"Study of Alpelisib (BYL719) in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy in Patients With HER2-positive Advanced Breast Cancer With a PIK3CA Mutation","route":"/trials/nct04208178/"},{"id":"nct05038735","kind":"trial","name":"Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-positive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.","route":"/trials/nct05038735/"}],"pairing":[{"id":"pi3k-pathway-plus-endocrine","kind":"pairing","name":"PI3K/AKT-pathway inhibitor + endocrine therapy (± CDK4/6)","route":"/pairings/pi3k-pathway-plus-endocrine/"}],"person":[{"id":"fabrice-andre","kind":"person","name":"Fabrice André","route":"/people/fabrice-andre/"},{"id":"sherry-lansing","kind":"person","name":"Sherry Lansing","route":"/people/sherry-lansing/"}],"paper":[{"id":"paper-solar-1-alpelisib-nejm-2019","kind":"paper","name":"SOLAR-1: alpelisib plus fulvestrant for PIK3CA-mutated hormone receptor-positive advanced breast cancer","route":"/key-papers/paper-solar-1-alpelisib-nejm-2019/"}],"drug":[{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}