{"entity":{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","aka":[],"tldr":"Adding capivasertib to first-line paclitaxel improved survival in metastatic triple-negative cancer from 12.6 to 19.1 months, with the largest gain in the fifth of patients whose tumours carried a PIK3CA, AKT1 or PTEN alteration.","summary":"140 women with untreated metastatic TNBC were randomised to paclitaxel 90 mg/m2 with capivasertib 400 mg twice daily (days 2 to 5, 9 to 12, 16 to 19) or placebo. Median PFS was 5.9 versus 4.2 months (HR 0.74; one-sided P 0.06 against a 0.10 threshold) and median overall survival 19.1 versus 12.6 months (HR 0.61). In 28 patients with PIK3CA/AKT1/PTEN-altered tumours PFS was 9.3 versus 3.7 months (HR 0.30). Grade 3 or worse diarrhoea 13% versus 1%.","asOf":"2026-09-24","links":[{"label":"Schmid et al., J Clin Oncol 2020: PAKT, capivasertib plus paclitaxel in 140 metastatic TNBC patients","url":"https://doi.org/10.1200/JCO.19.00368"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31841354/"}],"tags":[],"related":["pik3ca-hotspot-mutation","akt1-e17k","pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":[],"targets":["akt","pik3ca","pten"],"drugs":["capivasertib","paclitaxel"],"companies":["astrazeneca"],"institutions":[],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":[],"people":["peter-schmid"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2020,"doi":"10.1200/JCO.19.00368","pmid":"31841354","authors":"Schmid P, Abraham J, Chan S, et al.","paperType":"rct","findings":["PFS 5.9 versus 4.2 months (HR 0.74); overall survival 19.1 versus 12.6 months (HR 0.61).","PIK3CA/AKT1/PTEN-altered (28 of 140, 20%): PFS 9.3 versus 3.7 months (HR 0.30)."],"whatItMeans":"PAKT gives the trial-based prevalence of PI3K-pathway alteration in first-line metastatic TNBC (one in five) and the strongest signal for AKT inhibition in that subgroup; the phase 3 CAPItello-290 did not confirm it.","caveats":["Phase 2 with a lenient one-sided significance level.","Subgroup of 28 patients; CAPItello-290 was negative."],"changedPractice":false,"participants":140},"route":"/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/","neighbours":{"biomarker":[{"id":"akt1-e17k","kind":"biomarker","name":"AKT1 E17K mutation","route":"/biomarkers/akt1-e17k/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"},{"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":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}],"drug":[{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"}],"person":[{"id":"peter-schmid","kind":"person","name":"Peter Schmid","route":"/people/peter-schmid/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}