{"entity":{"id":"capitello-291","kind":"trial","name":"CAPItello-291","aka":[],"tldr":"Adding the AKT inhibitor capivasertib to fulvestrant doubled progression-free time, especially in tumours with PI3K-pathway mutations.","summary":"CAPItello-291, trial NCT04305496 sponsored by AstraZeneca and reported in 2022, showed that adding the AKT inhibitor capivasertib to fulvestrant doubled progression-free time in HR-positive, HER2-negative advanced breast cancer after an aromatase inhibitor, with the largest effect in tumours carrying PIK3CA, AKT1 or PTEN alterations. It randomised 708 women, about seventy percent of whom had received CDK4/6 inhibitors, met its primary progression-free survival endpoints in both the overall and the altered populations, and led to a 2023 FDA label restricted to the altered population, with diarrhoea, rash and hyperglycaemia as the main toxicities. OnCo links it to AKT and PIK3CA as targets, capivasertib, fulvestrant and Nicholas Turner. Final overall survival is awaited, and whether unaltered tumours benefit enough to widen the label is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04305496","url":"https://clinicaltrials.gov/study/NCT04305496"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":["kinase-inhibitors","pi3k-akt-mtor-inhibitors"],"targets":["akt","pik3ca"],"drugs":["capivasertib"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["nicholas-turner"],"bottlenecks":[],"keyPapers":["paper-capitello-291-nejm-2023"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04305496","phase":"3","setting":"HR+/HER2- advanced breast cancer after aromatase inhibitor (± CDK4/6): capivasertib + fulvestrant vs placebo + fulvestrant","sponsor":"AstraZeneca","result":"PFS HR 0.60 overall; HR 0.50 in AKT-pathway-altered.","started":"2020-04-16","startedType":"actual","yearReported":2022,"enrolled":708,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov lists 818 participants (actual); the NEJM 2023 primary analysis randomised 708 patients.","outcomes":[{"endpoint":"Progression-free survival (overall)","primary":true,"unit":"months","arms":[{"name":"Capivasertib + fulvestrant","n":355,"value":7.2},{"name":"Placebo + fulvestrant","n":353,"value":3.6}],"hr":0.6,"ci":[0.51,0.71],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2214131"},{"endpoint":"Progression-free survival (AKT-pathway-altered)","primary":true,"unit":"months","arms":[{"name":"Capivasertib + fulvestrant","n":155,"value":7.3},{"name":"Placebo + fulvestrant","n":134,"value":3.1}],"hr":0.5,"ci":[0.38,0.65],"p":"<0.001","source":"https://doi.org/10.1056/NEJMoa2214131"}],"replication":"Consistent with the phase 2 FAKTION trial (capivasertib + fulvestrant, PFS and OS benefit). Final OS from CAPItello-291 awaited."},"route":"/trials/capitello-291/","neighbours":{"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":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"drug":[{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"fulvestrant","kind":"drug","name":"Fulvestrant","route":"/drugs/fulvestrant/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"person":[{"id":"nicholas-turner","kind":"person","name":"Nicholas Turner","route":"/people/nicholas-turner/"}],"paper":[{"id":"paper-capitello-291-nejm-2023","kind":"paper","name":"CAPItello-291: capivasertib plus fulvestrant in hormone receptor-positive advanced breast cancer","route":"/key-papers/paper-capitello-291-nejm-2023/"}],"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/"}]}}