# 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

Source: https://onco.cc/key-papers/paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017/  
OnCo record `paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: The Lancet Oncology
- Year: 2017
- DOI: 10.1016/S1470-2045(17)30450-3
- Authors: Kim SB, Dent R, Im SA, et al.
- 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%.
- What it means: 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.

## Sources

- Kim et al., Lancet Oncol 2017: LOTUS, ipatasertib plus paclitaxel in 124 metastatic TNBC patients: https://doi.org/10.1016/S1470-2045(17)30450-3
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28800861/

## Connected records

- biomarkers: [PTEN alteration (sequencing) and PTEN loss (IHC)](https://onco.cc/biomarkers/pten-alteration/)
- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [AKT](https://onco.cc/targets/akt/), [PTEN](https://onco.cc/targets/pten/)
- drugs: [Ipatasertib](https://onco.cc/drugs/ipatasertib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- people: [Rebecca Dent](https://onco.cc/people/rebecca-dent/), [Sung-Bae Kim](https://onco.cc/people/kim-sung-bae/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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