Dr. Rugo on Pathway Blockade in Breast Cancer

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses pathway blockade in breast cancer.

Following the success of CDK4/6 inhibitors, Rugo says the next therapy to make an impact in the paradigm will be PI3K inhibitors. An alpha-specific inhibitor, alpelisib (BYL719) has the greatest promise of any of the PI3K inhibitors that have been studied to date, notes Rugo.

Though alpelisib shows some of the skin rash, hyperglycemia, and weight loss that has been seen with the more focused PI3K inhibitors, it does not have some of the other toxicities like colitis which makes it tough, as well as psychiatric issues and liver function test abnormalities.

A press release by Novartis suggested that the primary endpoint of improved progression-free survival was met in the SOLAR-1 trial, which randomized patients in the second-line setting to fulvestrant and placebo or alpelisib. Physicians need to see those data presented at the 2018 ESMO Congress, says Rugo, but she is hopeful that they will lead to the first approved PI3K inhibitor in the treatment of PI3K-mutant metastatic breast cancer.