The ALPHABET trial was officially launched in July 2021. This new study will enrol about 300 patients in approximately 110 hospitals from 6 European countries.
Its main objective is to test the efficacy and safety of the drug alpelisib, given in combination with trastuzumab (an anti-HER2 therapy), and compare this treatment with chemotherapy and trastuzumab.
This new treatment will be tested in patients with advanced HER2-positive breast cancer that is also positive for a PIK3CA mutation.
In some tumours, the PIK3CA gene, which contains the information needed to produce the PI3K protein, is abnormal (or mutated) and linked to cancer growth. Previous research suggests that mutations in the PIK3CA gene might lead to resistance to anti-HER2 therapy.
Treatment resistance is a common problem in patients with advanced HER2-positive breast cancer, and it can lead to the cancer coming back or continuing to grow.
ALPHABET is testing a new treatment strategy to overcome this resistance by combining the anti-HER2 therapy with alpelisib, a drug that blocks the PI3K protein and is known as a “PI3K inhibitor”.
The full scientific title of ALPHABET is “A randomised phase III trial of trastuzumab + ALpelisib +/- fulvestrant versus trastuzumab + chemotherapy in patients with PIK3CA mutated previously treated HER2+ Advanced BrEasT cancer”.
ALPHABET is an international study run and sponsored by GEICAM (the Spanish Breast Cancer Group) in collaboration with IBCSG (the International Breast Cancer Study Group) and the Breast International Group (BIG).