SABCS 2025: Evolving Role of CDK4/6 Inhibitors and SERDs in ER-Positive Breast Cancer

Kevin Kalinsky, MD, MS, FASCO Winship Cancer Institute of Emory University | Sarah Premji, MD Sarah Cannon Research Institute

December 18, 2025

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Key Points

  • Early progression on CDK4/6 inhibitors is a critical factor when selecting subsequent therapy in estrogen receptor (ER)–positive breast cancer, including evaluation for PIK3CA mutations.

  • Interim data showed promising efficacy with giredestrant, an oral selective estrogen receptor degrader (SERD), particularly for specific patients.

  • The growing pipeline of selective targeted therapies may reduce the reliance on chemotherapy in ER-positive disease.

The treatment-free interval and pattern of progression increasingly guide treatment decisions for patients with ER-positive breast cancer who relapse after receiving adjuvant CDK4/6 inhibitors. During a discussion at the 2025 San Antonio Breast Cancer Symposium (SABCS 2025), Kevin Kalinsky, MD, MS, FASCO, of Winship Cancer Institute of Emory University, and Sarah Premji, MD, of Sarah Cannon Research Institute, explored disease progression in patients on CDK4/6 inhibitors.

For patients whose disease progresses within a year, Dr. Kalinsky emphasized the importance of molecular reassessment, including testing for PIK3CA mutations. The experts also discussed the INAVO120 triplet versus doublet regimens in certain genomic subgroups.

A major highlight of SABCS 2025 was the role of giredestrant, with the interim analysis showing improvements in hazard ratios in the high 0.7 range and a modest overall survival benefit with this SERD. Although CDK4/6 inhibitors remain a backbone of therapy, giredestrant may be a reasonable option for patients who can’t tolerate that approach or are at particularly high risk, according to Dr. Kalinsky. However, the cost of giredestrant may be prohibitive.

Overall, Drs. Premji and Kalinsky expressed optimism about the growing number of selective targeted therapies entering the ER-positive breast cancer space, particularly in the metastatic setting. Emerging efficacy data offer hope for giving these therapies earlier in the disease course and ultimately reducing the need for chemotherapy.