Dr. Dent on Final LOTUS Findings in TNBC

Rebecca Dent, MD, senior consultant and head of Medical Oncology Department, National Cancer Center, Singapore, discusses the findings from the phase 2 LOTUS trial that treated patients with inoperable locally advanced/metastatic triple-negative breast cancer (TNBC) with first-line ipatasertib plus paclitaxel.

At the 2020 ESMO Breast Cancer Virtual Meeting, the data for the final overall survival (OS) outcomes in the phase 2 LOTUS trial were presented, says Dent; there are about 60 patients in each arm. The overall primary endpoint was PFS and researchers saw a prolonged benefit in the biomarker-positive population, as well as the intent-to-treat population. In the intent-to-treat population, ipatasertib/paclitaxel improved the median OS by 9 months, leading to a median OS of 25.8 months.

A phase 3 trial will be needed to confirm results; however, investigators saw a hazard ratio (HR) of .8 and an improvement of about 15% in 1-year OS.

When looking at the overall biomarker subset, which included PIK3CA/AKT1/PTEN mutations, as defined by next-generation sequencing, all of these showed numerical improvements in OS with the combination, but the numbers are too small at this point, Dent adds. Moreover, patients who were 50 years and older had an improvement in OS from 15 to 35 months, leading to a 60% reduction in the risk of death. This patient subgroup might be more susceptible to AKT inhibition but this is hypothesis generating, concludes Dent.