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 

 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.

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Rebecca Dent, MD, discusses the findings from the phase 2 LOTUS trial that treated patients with inoperable locally advanced/metastatic triple-negative breast cancer with first-line ipatasertib plus paclitaxel.

Dr. Dent on Final LOTUS Findings in TNBC

Rebecca Dent, MD, senior consultant, National Cancer Center, Singapore, discusses ipatasertib in the treatment of patients with triple-negative breast cancer (TNBC).

Ipatasertib is an oral AKT inhibitor that showed a promising trend toward improving overall survival (OS) in addition to paclitaxel in findings from the phase II LOTUS study of patients with locally advanced or metastatic TNBC. For patients who received ipatasertib plus paclitaxel, median OS was 23.1 months compared with 18.4 months for patients randomized to placebo plus paclitaxel.

Compared to some of the older AKT inhibitors, which are allosteric, ipatasertib has much better tolerability, Dent explains. Preclinical and early data have shown that blocking AKT is impactful in patients with 

mutations, those who have mutations upstream such as 

, says Dent. These are critical pathways in terms of survival for patients with breast cancer, as they are activated in about 40% of TNBC cases, she adds.

Rebecca Dent, MD, senior consultant, National Cancer Center, Singapore, discusses ipatasertib in the treatment of patients with triple-negative breast cancer.

Dr. Dent Discusses Ipatasertib in Triple-Negative Breast Cancer

Rebecca Dent, MD, senior consultant, National Cancer Center, Singapore, discusses the results of the LOTUS trial in patients with triple-negative breast cancer (TNBC).

The primary endpoint of the study was progression-free survival (PFS). There was modest improvement in the overall intent-to-treat population. However, researchers saw a big impact on PFS in the biomarker-positive group.

A panel was done by Foundation Medicine on either archived or fresh tissue that looked at 

. Patients with those alterations showed a 4- to 5-month improvement in PFS which Dent states is a fairly profound improvement in PFS in TNBC.

Researchers also looked at response, duration of response (DOR), and clinical benefit rate. The same trend was seen in terms of improved outcomes with ipatasertib, but the real benefit, says Dent, was seen in the DOR. The DOR almost doubled with the addition of ipatasertib in the biomarker-positive population. The phase III study is ongoing.

Rebecca Dent, MD, senior consultant, National Cancer Center, Singapore, discusses the results of the LOTUS trial in patients with triple-negative breast cancer.

Rebecca Dent, MD

Articles

Dr. Dent on Final LOTUS Findings in TNBC

Dr. Dent Discusses Ipatasertib in Triple-Negative Breast Cancer

Dr. Dent Discusses the LOTUS Trial in Triple-Negative Breast Cancer