Dr Kalinsky on the Importance of Novel Second-Line Therapies for HR+ Breast Cancer

“Additional endocrine-based treatments, along with targeted therapies, could improve how patients do post–CDK4/6 inhibition with endocrine therapy, which we commonly give as frontline therapy.”

Kevin Kalinsky, MD, MS, FASCO, professor and director in the Division of Medical Oncology in the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as the Louisa and Rand Glenn Family Chair in Breast Cancer Research and the director of the Glenn Family Breast Center at Winship Cancer Institute, discussed the need for additional research to improve treatment strategies in the post–CDK4/6 inhibitor setting for patients with advanced hormone receptor (HR)–positive breast cancer. He also noted factors that inform treatment selection following progression on a CDK4/6 inhibitor–based regimen in this patient population.

Kalinsky began by emphasizing the necessity for additional endocrine-based treatments in the HR-positive breast cancer treatment paradigm, which could enhance patient outcomes after prior CDK4/6 inhibition—a standard frontline treatment. The need for these advances is underscored by the persistent historical challenge associated with determining optimal second-line therapies, he said. In light of clinical data such as those from the phase 3 postMONARCH study (NCT05169567) of abemaciclib (Verzenio) plus fulvestrant (Faslodex) in advanced breast cancer following CDK4/6 inhibitor progression, achieving second-line treatment benefit lasting beyond 6 months remains a clinical challenge, he added.

What has generated considerable excitement, Kalinsky stated, is the observation of recent data demonstrating that this traditional 6-month efficacy threshold can often be surpassed through the strategic use of combination therapies. However, the selection of appropriate second-line therapy is highly individualized, according to Kalinsky, as these clinical decisions are influenced by several key factors.

One consideration involves assessing the cadence of disease progression, he continued. Oncologists must determine the duration of time the patient remained stable on the initial frontline therapy. Benefit for only a brief period raises concern regarding the true endocrine sensitivity of a patient’s tumor, he explained. In situations where endocrine sensitivity is questioned, pivoting toward a different treatment approach, such as the use of capecitabine or an antibody-drug conjugate, may be warranted, he concluded.