Academic Journal
CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial
| العنوان: | CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial |
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| المؤلفون: | Schettini, Francesco, Palleschi, Michela, Mannozzi, Francesca, Brasó-Maristany, Fara, Cecconetto, Lorenzo, Galván, Patricia, Mariotti, Marita, Ferrari, Alessia, Scarpi, Emanuela, Miserocchi, Anna, Nanni, Oriana, Sanfeliu, Esther, Prat, Aleix, Rocca, Andrea, De Giorgi, Ugo |
| المساهمون: | Schettini, Francesco, Palleschi, Michela, Mannozzi, Francesca, Brasó-Maristany, Fara, Cecconetto, Lorenzo, Galván, Patricia, Mariotti, Marita, Ferrari, Alessia, Scarpi, Emanuela, Miserocchi, Anna, Nanni, Oriana, Sanfeliu, Esther, Prat, Aleix, Rocca, Andrea, De Giorgi, Ugo |
| سنة النشر: | 2024 |
| المجموعة: | Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) |
| مصطلحات موضوعية: | CDK4/6-inhibitor, breast cancer, chemotherapy, hormone receptor, intrinsic subtype, tertiary lymphoid structures |
| الوصف: | Background: The optimal treatment approach for hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2-negative MBC) with aggressive characteristics remains controversial, with lack of randomized trials comparing cyclin-dependent kinase (CDK)4/6-inhibitors (CDK4/6i) + endocrine therapy (ET) with chemotherapy + ET. Materials and methods: We conducted an open-label randomized phase II trial (NCT03227328) to investigate whether chemotherapy + ET is superior to CDK4/6i + ET for HR+/HER2-negative MBC with aggressive features. PAM50 intrinsic subtypes (IS), immunological features, and gene expression were assessed on baseline samples. Results: Among 49 randomized patients (median follow-up: 35.2 months), median progression-free survival (mPFS) with chemotherapy + ET (11.2 months, 95% confidence interval [CI]: 7.7-15.4) was numerically shorter than mPFS (19.9 months, 95% CI: 9.0-30.6) with CDK4/6i + ET (hazard ratio: 1.41, 95% CI: 0.75-2.64). Basal-like tumors under CDK4/6i + ET exhibited worse PFS (mPFS: 11.4 months, 95% CI: 3.00-not reached [NR]) and overall survival (OS; mOS: 18.8 months, 95% CI: 18.8-NR) compared to other subtypes (mPFS: 20.7 months, 95% CI: 9.00-33.4; mOS: NR, 95% CI: 24.4-NR). In the chemotherapy arm, luminal A tumors showed poorer PFS (mPFS: 5.1 months, 95% CI: 2.7-NR) than other IS (mPFS: 13.2 months, 95% CI: 10.6-28.1). Genes/pathways involved in BC cell survival and proliferation were associated with worse outcomes, as opposite to most immune-related genes/signatures, especially in the CDK4/6i arm. CD24 was the only gene significantly associated with worse PFS in both arms. Tertiary lymphoid structures and higher tumor-infiltrating lymphocytes also showed favorable survival trends in the CDK4/6i arm. Conclusions: The KENDO trial, although closed prematurely, adds further evidence supporting CDK4/6i + ET use in aggressive HR+/HER2-negative MBC instead of chemotherapy. PAM50 IS, genomic, and immunological features are promising biomarkers to personalize therapeutic choices. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/38175669; info:eu-repo/semantics/altIdentifier/wos/WOS:001139056000001; volume:29; issue:5; firstpage:e622; lastpage:e634; numberofpages:13; journal:THE ONCOLOGIST; https://hdl.handle.net/11368/3067301; https://academic.oup.com/oncolo/article/29/5/e622/7510796?login=true |
| DOI: | 10.1093/oncolo/oyad337 |
| الاتاحة: | https://hdl.handle.net/11368/3067301 https://doi.org/10.1093/oncolo/oyad337 https://academic.oup.com/oncolo/article/29/5/e622/7510796?login=true |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.188E135C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/oncolo/oyad337 |
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