{"entity":{"id":"lotus","kind":"trial","name":"LOTUS","aka":[],"tldr":"LOTUS was the small trial that made the AKT-blocking tablet ipatasertib look promising in triple-negative breast cancer: added to paclitaxel it delayed progression by about six weeks. The larger IPATunity130 trial then failed to confirm it.","summary":"LOTUS (NCT02162719) randomised 124 women with measurable, untreated inoperable locally advanced or metastatic triple-negative breast cancer between September 2014 and February 2016 to paclitaxel 80 mg/m2 on days 1, 8 and 15 with ipatasertib 400 mg or placebo daily on days 1 to 21 of 28, stratified by prior neoadjuvant or adjuvant therapy, chemotherapy-free interval and PTEN status. The co-primary endpoints were progression-free survival in the intention-to-treat and PTEN-low populations. Median progression-free survival was 6.2 versus 4.9 months (stratified hazard ratio 0.60, 95 percent confidence interval 0.37 to 0.98, p 0.037) overall and 6.2 versus 3.7 months in the 48 patients with PTEN-low tumours (hazard ratio 0.59, 0.26 to 1.32, p 0.18); the largest effect was in tumours with PIK3CA, AKT1 or PTEN alterations, the group IPATunity130 then selected. Grade 3 or worse diarrhoea occurred in 23 percent of ipatasertib-treated patients against none on placebo. Its result, with PAKT for capivasertib, launched the two phase 3 AKT-inhibitor trials (IPATunity130, CAPItello-290) that both failed, so LOTUS is now read as an example of a phase 2 signal in a biomarker subgroup that did not replicate.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT02162719","url":"https://clinicaltrials.gov/study/NCT02162719"},{"label":"Kim et al., Lancet Oncology 2017: ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic TNBC (LOTUS)","url":"https://doi.org/10.1016/S1470-2045(17)30450-3"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["pi3k-akt-mtor-inhibitors","cytotoxic-chemotherapy"],"targets":["akt","pten","pik3ca"],"drugs":["ipatasertib","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":["ipatunity130","pakt","nct03997123"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02162719","phase":"2","setting":"Untreated inoperable locally advanced or metastatic triple-negative breast cancer: first-line paclitaxel with ipatasertib or placebo, 44 hospitals in eight countries","sponsor":"Genentech","result":"PFS 6.2 vs 4.9 months (HR 0.60, p 0.037); PTEN-low 6.2 vs 3.7 months (HR 0.59, p 0.18). Not confirmed by IPATunity130.","yearReported":2017,"enrolled":124,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival, intention to treat","primary":true,"unit":"months","arms":[{"name":"Ipatasertib + paclitaxel","n":62,"value":6.2},{"name":"Placebo + paclitaxel","n":62,"value":4.9}],"hr":0.6,"ci":[0.37,0.98],"p":"0.037","source":"https://doi.org/10.1016/S1470-2045(17)30450-3"},{"endpoint":"Progression-free survival, PTEN-low tumours","primary":true,"unit":"months","arms":[{"name":"Ipatasertib + paclitaxel","value":6.2},{"name":"Placebo + paclitaxel","value":3.7}],"hr":0.59,"ci":[0.26,1.32],"p":"0.18","source":"https://doi.org/10.1016/S1470-2045(17)30450-3"}],"replication":"Not replicated: IPATunity130 cohort A (PIK3CA/AKT1/PTEN-altered, 255 patients) showed no progression-free or overall survival benefit."},"route":"/trials/lotus/","neighbours":{"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"pi3k-akt-mtor-inhibitors","kind":"technology","name":"PI3K, AKT and mTOR inhibitors","route":"/technologies/pi3k-akt-mtor-inhibitors/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}],"drug":[{"id":"ipatasertib","kind":"drug","name":"Ipatasertib","route":"/drugs/ipatasertib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"trial":[{"id":"nct03997123","kind":"trial","name":"Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC","route":"/trials/nct03997123/"},{"id":"ipatunity130","kind":"trial","name":"IPATunity130","route":"/trials/ipatunity130/"},{"id":"pakt","kind":"trial","name":"PAKT","route":"/trials/pakt/"}]}}