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William J. Gradishar, MD, FACP, FASCO

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CKD4/6 Inhibition and Endocrine Therapy vs Chemotherapy for Metastatic Breast Cancer

By: Joshua D. Madera, MD
Posted: Wednesday, February 28, 2024

The combination of a CDK4/6 inhibitor and endocrine therapy for metastatic breast carcinoma may be a suitable alternative, according to the results of the phase II KENDO study, published in The Oncologist. Additional investigative efforts focused on identifying biomarkers that may enable personalized therapy are warranted, suggested Francesco Schettini, MD, PhD, of the August Pi I Sunyer Biomedical Research Institute, Barcelona, and colleagues.

“Exploratory biomarker analyses suggested a potential role for biological tumor features (eg, PAM50 intrinsic subtypes, risk of relapse and proliferation) and microenvironment immunologic composition (eg, tumor-infiltrating lymphocytes and tertiary lymphoid structures) in guiding therapeutic choices in this context,” the investigators noted. “CD24 seemed to be a potential therapeutic target.”

A total of 49 patients with hormone receptor–positive, HER2-negative metastatic breast cancer were recruited for the study. Patients were randomly assigned to receive treatment with a CKD4/6 inhibitor (palbociclib, ribociclib, abemaciclib) plus endocrine therapy (arm A, n = 17) or endocrine therapy plus chemotherapy (arm B, n = 32). Breast tissue samples were collected at baseline, and genomic analyses were performed to determine receptor status. 

The study authors reported a significantly increased median progression-free survival (hazard ratio = 1.41) for patients in arm A (19.9 months) compared with patients in arm B (11.2 months). Patients in arm A with basal-like tumors demonstrated the worst progression-free survival (11.4 months) and overall survival rates (18.8 months) compared with those who had other tumor subtypes. Patients in arm B with luminal tumors had a poorer progression-free survival (5.1 months) than did those who had other intrinsic subtypes. Furthermore, a worse progression-free survival was significantly associated with the expression of CD24, regardless of the type of treatment patients received. Moreover, improved survival trends were observed in patients from arm A who had tertiary lymphoid structures and higher tumor-infiltrating lymphocytes.

Disclosure: For full disclosures of the study authors, visit academic.oup.com.


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