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
; 29(5): e622-e634, 2024 May 03.
Article
em En
| MEDLINE
| ID: mdl-38175669
ABSTRACT
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)â +â endocrine therapy (ET) with chemotherapyâ +â ET. MATERIALS ANDMETHODS:
We conducted an open-label randomized phase II trial (NCT03227328) to investigate whether chemotherapyâ +â ET is superior to CDK4/6iâ +â 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 chemotherapyâ +â 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 CDK4/6iâ +â ET (hazard ratio 1.41, 95% CI 0.75-2.64). Basal-like tumors under CDK4/6iâ +â 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 CDK4/6iâ +â ET use in aggressive HR+/HER2-negative MBC instead of chemotherapy. PAM50 IS, genomic, and immunological features are promising biomarkers to personalize therapeutic choices.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Biomarcadores Tumorais
/
Receptor ErbB-2
/
Quinase 4 Dependente de Ciclina
/
Quinase 6 Dependente de Ciclina
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Oncologist
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Espanha