Get down LOTUS.

August 18, 2017. The PI3K/AKT pathway is a popular target in cancer research since its activation is frequently a main driver of proliferation. Especially in triple negative breast cancer (TNBC), a subtype which, unlike the others, has not seen many recent advancements in treatment options. The LOTUS trial now out in Lancet Oncology puts all that theoretical science to a real-world test. It randomized women with previously untreated locally-advanced or metastatic TNBC to paclitaxel +/- ipatasertib. Ipatasertib is a small molecule that competes with ATP for binding sites on Akt, which is a middle-man for PI3K activation of the mTOR pathway. While ipatasertib caused a lot of extra diarrhea and neutropenia, it improved median progression free survival from 4.9 to 6.2 months. This represents a two-fold victory: clinical control of a difficult-to-control pathway...and a difficult-to-control disease. But don’t eat from the lotus tree just yet. We still have a long way to go in achieving a tolerable treatment with substantial survival benefits for our TNBC patients.