How effective is alpelisib in hormone-receptor positive breast cancer with PIK3CA-mutations?

This study investigated the effectiveness of alpelisib (Piqray) in hormone receptor-positive (HR+) -human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC).

They found that alpelisib significantly improved survival in patients with PIK3CA mutations. 

Breast cancer (BC) types can be categorized according to the proteins or receptors that BC tumors express. The majority of BC tumors are positive for hormone receptor (HR+) and negative for human epidermal growth factor receptor-2 (HER2-). Using drugs that target these receptors can improve outcomes. Endocrine therapy is a standard treatment for HR+/HER2- BC. However, some BC tumors can become resistant to treatment. 

Approximately 40% of HR+/HER2- BC tumors also express mutations in a gene called PIK3CA. This leads to overactivity of the PI3K enzyme and disrupts normal cell signaling to allow cancer cells to grow. Alpelisib is a new drug that blocks PIK3 activity. It is unclear if alpelisib is effective in treating HR+/HER- BC with PI3KCA mutations. 

This study included 572 patients with advanced HR+/HER2- BC. 341 patients had PI3KCA mutations. Patients were randomly assigned to treatment with alpelisib (169) or placebo (172). All patients were also treated with fulvestrant (Faslodex). Fulvestrant is a standard drug for treating HR+ BC. The main outcome was progression-free survival (PFS; survival without cancer growing or spreading). 

After an average time of 20 months, in patients with PI3KCA-mutations, alpelisib + fulvestrant resulted in a PFS of 11 months. This was compared to 5.7 months in the placebo + fulvestrant group. The overall response to treatment was better in alpelisib group (26.6% vs. 12.8%). The risk of disease progression was 35% lower in alpelisib-treated patients.

Patients without PI3KCA-mutations had a slightly higher PFS when treated with alpelisib when compared to placebo (7.4 months vs 5.6 months). Side effects included high blood sugar, diarrhea, nausea, decreased appetite, and rash. 

The authors concluded that alpelisib significantly improved survival in patients with HR+ BC and PIK3CA mutations.

This trial served as bases for the FDA approval of alpelisib in combination with fulvestrant for postmenopausal women, and men, with HR+, HER2-, PIK3CA-mutated, advanced or metastatic BC.

This study was funded by Novartis, the manufacturer of alpelisib.