Alpelisib showed improvement in progression-free survival in the global phase III SOLAR-1 trial.

The phosphoinositide 3-kinase (PI3K) pathway is a signaling pathway that is commonly activated in many different cancers. The alteration of the PI3K regulation of cellular processes can result in cancer progression via modification of cell metabolism, growth, survival and motility.

In HR+ advanced breast cancer, the PI3K pathway is the most frequently altered pathway promoting tumor growth, disease progression and treatment resistance. There are four isoforms of proteins in the PI3K pathway. Of HR+ advanced breast cancer patients, 40% have PIK3CA mutations that activate the alpha isoform. Mutations in the three other isoforms are typically not associated with advanced breast cancer. 

To date, no PI3K inhibitors for HR+ advanced breast cancer have been approved. However, Novartis is developing the first alpha-specific PI3K inhibitor. The orally bioavailable BYL719 (alpelisib) has been shown to potentially inhibit the PI3K pathway and have antiproliferative effects in breast cancer cell lines harboring PIK3CA mutations.

The company recently reported positive results for the global phase III SOLAR-1 trial evaluating BYL719. The study met its primary endpoint with respect to improvement in progression-free survival (PFS) for patients treated with BYL719, in combination with the selective estrogen receptor degrader (SERD) Fulvestrant — compared to those treated only with Fulvestrant.

Patients in the study included postmenopausal women and men with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) PIK3CA-mutant advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor.