Joyce A. O’Shaughnessy, MD
A novel inhibitor that targets the AKT node in the PI3K pathway may offer a treatment option in cases of resistance to chemotherapy in 2 patient populations: triple-negative breast cancer (TNBC) or estrogen receptor (ER)– positive, HER2-negative breast cancer with certain molecular aberrations. The agent, ipatasertib, is being tested in combination with paclitaxel in the randomized phase II/III IPATunity130 clinical trial (NCT03337724).
Figure. Ipatasertib in Breast Cancer Subtypes
“AKT is a master regulator of survival within the cancer cell and can lead the cell to repair DNA, for example, as 1 mechanism of chemotherapy resistance. When [the patient has cancer with] a PIK3CA mutation, the odds of achieving a pathological complete response are considerably less,” O’Shaughnessy explained. Prior trial results have confirmed the value of combining ipatasertib and paclitaxel for patients who have the relevant gene alterations. The multicenter, randomized, phase II LOTUS trial looked at PFS overall and in patients with low PTEN expression, but the study also examined overall survival in patients with PI3K/AKT pathwayactivated tumors as a secondary endpoint. There was a PFS benefit observed in both subtypes favoring the combination of ipatasertib and paclitaxel.
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