Targeting PIK3CA Mutations in Breast Cancer

Andreas Varkaris, MD, PhD, attending physician and investigator, Termeer Center for Targeted Therapies, Massachusetts General Hospital, talks about targeting PIK3 signaling in breast cancer and the novel therapies being developed to treat these tumors.

Due to the prevalence of PIK3CA mutations in patients with breast cancer, especially in those with hormone-receptor, HER2-negative disease, many agents are under clinical development to improve outcomes for patients with PIK3CA-mutated breast cancer. There is only 1 drug currently FDA-approved to treat these patient, alpelisib (Piqray), which underscores the need for new drugs.

Varkaris says that newer studies are even beginning to look at PI3K inhibitors in combination with other effective agents to improve the chances of good outcomes for patients with PIK3CA-mutated breast cancer. This includes a phase 1 study for which Varkaris is an investigator, (ReDiscover; NCT05216432).

Transcript:

0:09 | PIK3CA mutations are relatively common. They're seen in 14% of all solid tumors. But there are some subtypes of solid tumors that we find PIK3CA more commonly, for example, breast cancer tumors, especially hormone receptor-positive/ HER2-negative, advanced breast cancer tumors, express PIK3CA mutations in up to 40% of the cases. In the past, we have been able to treat these patients with altered generations of PI3K inhibitors. We have an FDA approved drug called alpelisib, which is equally potent against the mutant, the wild-type enzyme, and has prolonged the life of patients with metastatic breast cancer with these mutations.

1:00 | We look forward to a new generation of inhibitors that will allow us to inhibit the enzyme more potently, without affecting the normal cells, and increase the number of patients that we will be able to treat. Also, by having more targeted therapies, we'll be able to combine these new drugs with other targeted therapies, something that wasn't feasible in the past because of the toxicity profile.