Ipatasertib May Prolong PFS in Triple-negative Breast Cancer

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Researchers randomly assigned 124 patients to receive intravenous paclitaxel with ipatasertib or placebo.
Researchers randomly assigned 124 patients to receive intravenous paclitaxel with ipatasertib or placebo.

Ipatasertib, an oral AKT inhibitor, may prolong progression-free survival (PFS) among patients with triple-negative breast cancer, according to a study published in The Lancet Oncology.1

The activity of the PI3K/AKT signaling pathway, which promotes cell survival and growth in cancers, suggests it is a target for therapy in patients with breast cancer.

The phase 2 LOTUS trial (ClinicalTrials.gov Identifier: NCT02162719) is the first prospective trial to target AKT in triple-negative breast cancer. Researchers randomly assigned 124 patients to receive intravenous (IV) paclitaxel 80 mg/m2 with ipatasertib 400 mg or placebo.

The median follow-up was 10.2 months in the placebo group vs 10.4 months in the ipatasertib group.

Patients in the ipatasertib arm had a median PFS of 6.2 months (95% CI, 3.8-9.0) vs 4.9 months (95% CI, 3.6-5.4) among patients in the placebo arm (hazard ratio [HR], 0.60; 95% CI, 0.37-0.98; P = .037).

Median PFS in patients with PTEN-low tumors was 6.2 months (95% CI, 3.6-9.1) in the ipatasertib group vs 3.7 months (95% CI, 1.9-7.3) in the placebo group (HR, 0.59; 95% CI, 0.26-1.32; P = .18).

The most frequently reported grade 3 or worse adverse events (AEs) in the treatment group vs placebo, respectively, were diarrhea (23% vs 0%), decreased neutrophil count (8% vs 6%), and neutropenia (10% vs 2%). Overall, serious AEs were reported in 28% of patients receiving ipatasertib and 15% of the placebo group.

RELATED: Q&A With Adam M. Brufsky, MD, PhD: Endocrine-based Therapy for HR-positive Metastatic Breast Cancer

The authors concluded that these “findings warrant further prospective investigation of ipatasertib in the population of patients with PIK3CA/AKT1/PTEN-altered tumors.”


  1. Kim SB, Dent R, Im SA, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomized, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Aug 8. doi: 10.1016/S1470-2045(17)30450-3 [Epub ahead of print]

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