Dr. Tolaney on Sequencing Questions in Breast Cancer

Sara M. Tolaney, MD, MPH, associate director of the Susan F. Smith’s Center for Women’s Cancers, director of Clinical Trials, Breast Oncology, senior physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses remaining sequencing questions in breast cancer.

Many sequencing questions remain in the breast cancer space, says Tolaney. For example, the question of what should be done when a patient started on endocrine therapy and a CDK4/6 inhibitor progresses has yet to be answered. It remains unclear whether the CDK4/6 inhibitor should be continued and the endocrine backbone should be swapped out, adds Tolaney. Additionally, the question of whether it would be beneficial to continue CDK4/6 inhibition beyond progression in these patients also remains open. However, ongoing trials are seeking to address these questions, says Tolaney.

For example, the PACE trial is enrolling patients who have progressed on up-front CDK4/6 inhibition. In the trial, patients are being randomized to receive either fulvestrant (Faslodex) alone, fulvestrant with palbociclib (Ibrance), or fulvestrant with palbociclib and avelumab (Bavencio). Investigators are looking for synergistic activity with immunotherapy, explains Tolaney.

Another question within the space is whether it would make a difference if the CDK4/6 inhibitor were swapped out as well, says Tolaney. For example, if a patient was treated with up-front palbociclib or ribociclib (Kisqali) and then they were switched over to abemaciclib (Verzenio) in the second-line setting, would that agent have more benefit than continuing the same CDK4/6 inhibitor? Some small trials are aiming to address that question, says Tolaney.

One trial is specifically examining patients who were treated with an aromatase inhibitor and palbociclib, continued the same endocrine agent, and swapped the CDK4/6 inhibitor with abemaciclib at the time of disease progression. This trial will shed light on whether switching a CDK4/6 inhibitor will benefit patients, concludes Tolaney.