Redefining Breast Cancer Treatment: New Insights from the KENDO Trial

Study Overview

The study titled "CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial" was an open-label, randomized phase II trial (1). The population under investigation included patients with hormone receptor-positive/HER2-negative metastatic breast cancer. The intervention investigated was the comparison between chemotherapy plus endocrine therapy (ET) and CDK4/6-inhibitors plus ET.

The control group received chemotherapy plus endocrine therapy, while the intervention group received CDK4/6-inhibitors plus endocrine therapy. The study enrolled 49 patients. The results indicated that median progression-free survival (PFS) with chemotherapy plus ET was shorter (11.2 months) compared to CDK4/6-inhibitors plus ET (19.9 months). Basal-like tumors under CDK4/6-inhibitors plus ET exhibited worse PFS and overall survival compared to other subtypes. Conversely, luminal A tumors in the chemotherapy arm showed poorer PFS than other intrinsic subtypes.

In summary, the study adds evidence supporting the use of CDK4/6-inhibitors plus ET in aggressive HR+/HER2-negative metastatic breast cancer over chemotherapy. PAM50 intrinsic subtypes, genomic, and immunological features emerged as promising biomarkers for personalizing therapeutic choices.

Standard Treatment

The standard treatment for hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer typically involves a combination of endocrine therapy and targeted treatments. Endocrine therapy, which includes drugs like aromatase inhibitors (e.g., letrozole, anastrozole, exemestane), selective estrogen receptor modulators (e.g., tamoxifen), and selective estrogen receptor degraders (e.g., fulvestrant), is a cornerstone of treatment for these types of breast cancers. Additionally, the use of CDK4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib) in combination with endocrine therapy has become a standard approach due to their effectiveness in improving progression-free survival. Treatment decisions are tailored based on various factors including menopausal status, prior therapies, and the presence of specific tumor characteristics.

Clinical Impact Potential

The clinical impact potential of this trial can be considered medium. The study provides valuable insights into the efficacy of CDK4/6 inhibitors in combination with endocrine therapy, compared to chemotherapy plus endocrine therapy, in treating HR+/HER2- metastatic breast cancer. This could influence treatment strategies for a specific subset of breast cancer patients. However, being a phase II trial with a relatively small sample size limits the immediate applicability of its findings to broader clinical practice. Further research, particularly large-scale phase III trials, is necessary to confirm these results and potentially alter standard treatment guidelines.

Reference

Schettini F, Palleschi M, Mannozzi F, Brasó-Maristany F, Cecconetto L, Galván P, Mariotti M, Ferrari A, Scarpi E, Miserocchi A, Nanni O, Sanfeliu E, Prat A, Rocca A, De Giorgi U. CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial. Oncologist. 2024 Jan 4:oyad337. doi: 10.1093/oncolo/oyad337. Epub ahead of print. PMID: 38175669.