{"entity":{"id":"paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","kind":"paper","name":"Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","aka":[],"tldr":"Adding the AKT inhibitor ipatasertib to first-line paclitaxel lengthened the time before metastatic triple-negative cancer grew from 4.9 to 6.2 months, the first randomised support for AKT-directed therapy in the disease.","summary":"124 women with untreated inoperable locally advanced or metastatic TNBC were randomised to paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo, stratified by prior therapy, chemotherapy-free interval and tumour PTEN status. Median progression-free survival was 6.2 versus 4.9 months (stratified HR 0.60, 95% CI 0.37 to 0.98) in the intention-to-treat population and 6.2 versus 3.7 months (HR 0.59, 0.26 to 1.32) in the 48 PTEN-low patients. Grade 3 or worse diarrhoea occurred in 23% with ipatasertib.","asOf":"2026-09-24","links":[{"label":"Kim et al., Lancet Oncol 2017: LOTUS, ipatasertib plus paclitaxel in 124 metastatic TNBC patients","url":"https://doi.org/10.1016/S1470-2045(17)30450-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28800861/"}],"tags":[],"related":["pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["akt","pten"],"drugs":["ipatasertib","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":[],"people":["kim-sung-bae","rebecca-dent"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2017,"doi":"10.1016/S1470-2045(17)30450-3","pmid":"28800861","authors":"Kim SB, Dent R, Im SA, et al.","paperType":"rct","findings":["PFS 6.2 versus 4.9 months (HR 0.60) in all patients.","PTEN-low (48 patients): 6.2 versus 3.7 months (HR 0.59, not significant).","Grade 3 diarrhoea 23%."],"whatItMeans":"LOTUS and PAKT together made the PI3K/AKT/PTEN-altered subgroup the target population for AKT inhibitors in TNBC; the phase 3 IPATunity130 later failed to confirm it, which is why no AKT inhibitor is approved here.","caveats":["Phase 2 with 124 patients; PTEN by immunohistochemistry.","IPATunity130 (phase 3) did not confirm the benefit."],"changedPractice":false,"participants":124},"route":"/key-papers/paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017/","neighbours":{"biomarker":[{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","route":"/biomarkers/pten-alteration/"}],"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/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"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/"}],"person":[{"id":"rebecca-dent","kind":"person","name":"Rebecca Dent","route":"/people/rebecca-dent/"},{"id":"kim-sung-bae","kind":"person","name":"Sung-Bae Kim","route":"/people/kim-sung-bae/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}