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.
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Citations
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References
Predictive Biomarker Profiling of > 6000 Breast Cancer Patients Shows Heterogeneity in TNBC, With Treatment Implications.
A double-blind, randomised, placebo-controlled, phase 2b study evaluating sorafenib in combination with paclitaxel as a first-line therapy in patients with HER2-negative advanced breast cancer.
Evaluation and Clinical Analyses of Downstream Targets of the Akt Inhibitor GDC-0068
Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer
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Frequently Asked Questions (7)
Q2. What were the common adverse events in the LOTUS trial?
The most common grade 3 or worse adverse events were diarrhoea (14 [23%] of 61 ipatasertib-treated patients vs none of 62 placebo-treated patients), neutrophil count decreased (five [8%] vs four [6%]), and neutropenia (six [10%] vs one [2%]).
Q3. What was the primary endpoint of the LOTUS trial?
The co-primary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low (by immunohistochemistry) population.
Q4. What is the main purpose of the study?
The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer.
Q5. How many patients were enrolled in the LOTUS trial?
In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium.
Q6. How many patients were randomly assigned to ipatasertib?
Enrolled patients were randomly assigned (1:1) to receive intravenous paclitaxel 80 mg/m² (days 1, 8, 15) with either ipatasertib 400 mg or placebo once per day (days 1–21) every 28 days until disease progression or unacceptable toxicity.
Q7. How long did the LOTUS trial last?
Median progression-free survival in the intention-to-treat population was 6·2 months (95% CI 3·8–9·0) with ipatasertib versus 4·9 months (3·6–5·4) with placebo (stratified hazard ratio [HR] 0·60, 95% CI 0·37–0·98; p=0·037) and in the 48 patients with PTEN-low tumours, median progression-free survival was 6·2 months (95% CI 3·6–9·1) with ipatasertib versus 3·7 months (1·9–7·3) with placebo (stratified HR 0·59, 95% CI 0·26–1·32, p=0·18).