Dr. Rugo on Resistance to CDK4/6 Inhibitors in HR+ Breast Cancer

Hope Rugo, MD, professor of medicine, director of the Breast Oncology Clinical Trials Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses resistance to CDK4/6 inhibitors in hormone receptor (HR)-positive breast cancer.

Physicians are actively trying to understand resistance to CDK4/6 inhibitors, both in upfront and acquired subpopulations, says Rugo. In the PALOMA studies, it has been difficult to identify a subpopulation that does not benefit from these drugs with the possible exception of patients who have upfront mutations in the Rb gene.

In looking at acquired resistance or potentially upfront mechanisms of resistance in patients, mutated cyclin E has emerged as an interesting biomarker of resistance. A higher concentration of cyclin E may be the reason why the tumor can overcome the effect of CDK4/6 inhibitors, notes Rugo.

Other mechanisms have been studied and have shown promising data with FGFR overexpression. A number of trials are looking at ways to overcome those mechanisms, says Rugo, some of which are trying to incorporate the use of cell-free DNA as a way to identify them.