Dr. Goetz on Treatment Beyond Progression on CDK4/6 Inhibitors in HR+ Breast Cancer

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses treatment beyond progression on CDK4/6 inhibitors in hormone receptor (HR)-positive breast cancer.

The prognosis of patients who progress on CDK4/6 inhibitors remains largely unknown. However, there are emerging data that suggest that the prognosis of patients who go on to receive standard endocrine therapy, such as tamoxifen (Faslodex) or an aromatase inhibitor, do poorly, says Goetz. Whether CDK4/6 inhibitors should be continued beyond progression is another area of uncertainty, he adds.

Better understandings of the mechanisms of resistance driving progression will be critical in answering such questions. Moving forward, clinical trials will be focused examining these agents in specific subsets of patients. One of the first clinical trials to do so was the phase III SOLAR-1 trial, in which patients with HR-positive, HER2-negative advanced breast cancer who had received prior endocrine therapy were randomized to receive either alpelisib (Piqray) and fulvestrant or fulvestrant alone. Patients were stratified by PIK3CA mutation status. Results showed that those who harbored PIK3CA mutations derived a significant clinical benefit from the combination.

Data from the phase II BYLieve trial will help establish whether fulvestrant or letrozole is the optimal combination partner for alpelisib. Ultimately, many therapeutic strategies will be needed to overcome the number of resistance mutations that develop after progression on a CDK4/6 inhibitor, concludes Goetz.