Dr O’Regan on Sequencing Considerations in Advanced HR+ Breast Cancer

We don’t have a clear sequence approach [at this point]; however, what’s going to happen is most patients are going to get most of these agents during the course of their disease. It is exciting because we have so many new agents.”

Ruth M. O’Regan, MD, professor, chair, Charles Ayrault Dewey Professorship of Medicine, Department of Medicine, the University of Rochester, physician-in-chief, Strong Memorial Hospital, associate director, Education and Mentoring, the Wilmot Cancer Institute at the University of Rochester, discusses the treatment sequencing strategies for patients with hormone receptor (HR)–positive breast cancer.

O’Regan highlighted these considerations during a presentation at the 42nd Annual Chemotherapy Foundation Symposium (CFS) hosted by Physicians’ Education Resource, LLC.

In HR-positive breast cancer, treatment selection depends on the presence of actionable mutations, prior therapies, and disease progression, O’Regan explains. After receiving frontline treatment with a CDK4/6 inhibitor–based treatment, patients without actionable mutations could be switched to a different CDK4/6 inhibitor in combination with endocrine therapy, or treated with everolimus (Zortress) plus endocrine therapy or an antibody-drug conjugate, she continues.

Treatment selection after first-line progression for patients with tumors harboring actionable mutations involves genomic profiling to inform therapeutic strategies, O’Regan continues. For example, patients with PIK3CA mutations can be treated with targeted agents such as alpelisib (Piqray), capivasertib (Truqap) plus fulvestrant (Faslodex), or inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant. Capivasertib plus fulvestrant is also indicated for patients with AKT1 or PTEN alterations, she adds.. Additionally, for tumors harboring ESR1 mutations, the oral selective estrogen receptor degrader (SERD) elacestrant is an approved option after at least 1 line of endocrine therapy. These therapies reflect the growing emphasis on molecularly guided treatment, O’Regan says.

Although there are not clear data to inform sequencing of these various agents in patients who may be eligible for more than 1 targeted therapy; however, O’Regan concludes that the growth of treatment options in the later-line settings of HR-positive breast cancer has been encouraging.