Sung-Bae Kim, MD
The randomized phase II LOTUS trial has shown improved progression-free survival with the addition of the AKT inhibitor ipatasertib to paclitaxel in the first-line treatment of metastatic triple-negative breast cancer. These results were reported by Sung-Bae Kim, MD, of the University of Ulsan College of Medicine, Seoul, and colleagues in The Lancet Oncology. The PI3K/AKT signaling pathway is frequently activated in triple-negative breast cancer.
In the double-blind trial, 124 patients with unresectable locally advanced or metastatic disease from 44 sites in South Korea, the United States, France, Spain, Taiwan, Singapore, Italy, and Belgium were randomized between September 2014 and February 2016 to receive paclitaxel at 80 mg/m2 on days 1, 8, and 15 with either ipatasertib at 400 mg (n = 62) or placebo (n = 62) once daily on days 1 to 21 every 28 days until disease progression or unacceptable toxicity. The coprimary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low population.
Progression-Free Survival and Adverse Events
Median follow-up was 10.4 months in the ipatasertib group and 10.2 months in the placebo group. Median progression-free survival was 6.2 months with ipatasertib vs 4.9 months with placebo in the intention-to-treat population (stratified hazard ratio [HR] = 0.60, P = .037) and 6.2 months vs 3.7 months among the 48 patients with PTEN-low tumors (stratified HR = 0.59, P = .18).
The most common grade ≥ 3 adverse events were diarrhea (23% in the ipatasertib group, all grade 3, vs 0% of the placebo group), neutropenia (10% vs 2%), and decreased neutrophil count (8% vs 6%). Serious adverse events occurred in 28% of the ipatasertib group (primarily infections and gastrointestinal effects) vs 15% of the placebo group (primarily infections).
The investigators concluded: “Progression-free survival was longer in patients who received ipatasertib than in those who received placebo. To our knowledge, these are the first results supporting AKT-targeted therapy for triple-negative breast cancer. Ipatasertib warrants further investigation for the treatment of triple-negative breast cancer.”■