by Dr. C.H. Weaver M.D. 2/2020
The addition of the AKT inhibitor capivasertib to first-line paclitaxel delays breast cancer progression and prolongs survival in women with previously untreated, metastatic triple-negative breast cancer (TNBC), according to results of the phase 2 PAKT clinical trial.
Capivasertib is an orally available precision cancer medicine that inhibits the serine/threonine protein kinase AKT. A wide range of cancers show dysregulated PI3K/AKT/mTOR signaling due to mutations in multiple signaling components. By targeting AKT, a key component in the PIK3/AKT signaling network, capivasertib can decrease cancer cell growth and spread. The PI3K/AKT pathway is frequently activated in TNBC and is associated with resistance to chemotherapy
About the PAKT Clinical Trial
In this clinical study 140 women with advanced TNBC were treated with paclitaxel chemotherapy without or without capivasertib as first-line therapy in women with previously untreated, metastatic TNBC and directly compared. The majority of women had previously failed adjuvant or neoadjuvant chemotherapy, including prior taxane-based therapy in over 50% of the patients.
With a median follow-up of 18.2 months the median duration without cancer progression was 5.5 months in the capivasertib treated patients compared to 3.6 months for those treated with chemotherapy only. The average survival duration was 19.1 months in the capivasertib group compared with 12.6 months for those treated with chemotherapy without capivasertib.
Among the subgroup of women with PIK3CA/AKT1/PTEN-altered tumors the median time to cancer progression was 9.3 months with capivasertib compared to only 3.7 months for paclitaxel chemotherapy alone. The median duration of response was 13.3 months with capivasertib in women with PIK3CA/AKT1/PTEN mutations.
The addition of the AKT inhibitor capivasertib improves the outcome of first-line paclitaxel chemotherapy with the bulk of the benefit observed in patients with certain mutations in their tumor, including AKT, PIK3CA or PTEN.