# LOTUS

Source: https://onco.cc/trials/lotus/  
OnCo record `lotus` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Registry id: 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
- Enrolled: 124
- 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.
- Outcomes: Progression-free survival, intention to treat: Ipatasertib + paclitaxel 6.2 months vs Placebo + paclitaxel 4.9 months, HR 0.6; Progression-free survival, PTEN-low tumours: Ipatasertib + paclitaxel 6.2 months vs Placebo + paclitaxel 3.7 months, HR 0.59
- Replication: Not replicated: IPATunity130 cohort A (PIK3CA/AKT1/PTEN-altered, 255 patients) showed no progression-free or overall survival benefit.

## Sources

- ClinicalTrials.gov NCT02162719: https://clinicaltrials.gov/study/NCT02162719
- Kim et al., Lancet Oncology 2017: ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic TNBC (LOTUS): https://doi.org/10.1016/S1470-2045(17)30450-3

## Connected records

- cancers: [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/)
- targets: [AKT](https://onco.cc/targets/akt/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/), [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/)
- trials: [Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC](https://onco.cc/trials/nct03997123/), [IPATunity130](https://onco.cc/trials/ipatunity130/), [PAKT](https://onco.cc/trials/pakt/)

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