What is the anti-tumor effect of Apelvis?

Alpelisib (Alpelisib) is a new therapy approved for patients with HR-positive, HER2-negative breast cancer who have progressed on first-line hormone therapy. Apelix's novel mechanism selectively inhibits the PI3K pathway, a driver mutation found in HR-positive, HER2-negative breast cancer. It is known that constitutive activation of PI3K signaling is a critical step in mediating the transforming potential of oncogenes and tumor suppressors in many tumor types. Mutations in this gene are found in many types of cancer, including breast, ovarian, lung, brain and stomach cancers.

Research has begun on apelix, a PI3K inhibitor that selectively targets the p110-alpha isoform of the protein Apelvis selectively binds the alpha isoform 50 times more efficiently than other isoforms found in this pathway. In May 2019, the U.S. Food and Drug Administration (FDA) approved apelvis in combination with fulvestrant for the treatment of HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer that has made progress in hormonal therapy.

In clinical studies, the efficacy of apelvis plus fulvestrant showed a median PFS of 11.0 months, compared with 5.7 months in the placebo group. At 12 months, the percentage of patients with PFS was 46.3% for apelvis and fulvestrant and 32.9% for placebo and fulvestrant. Overall responses were greater across all patients in the trial, as were clinical benefits and tumor responses compared with placebo and fulvestrant. When comparing these results to a cohort without PIK3CA mutations, a significant improvement in progression-free survival (PFS) was seen in patients with PIK3CA mutations. The median PFS for apelvis and fulvestrant was 7.4 months (95% CI, 5.4-9.3), and at 12 months, the PFS was 28.4%.

These results show that adding apelvis to PIK3CA-mutated, HR-positive, HER2-negative advanced cancer nearly doubled patient outcomes. These findings validate the use of PI3K as an important therapeutic target in patients who progress on endocrine therapy.