Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials

Francisco Cezar Aquino de Moraes; Gustavo de Oliveira Almeida; Vinícius Freire Costa Alves; Jonathan N Priantti; Giovanna da Conceição Gomes; Sarah Vitória Bristot Carnevalli; Thiago Madeira; Maysa Vilbert; Carlos Stecca; Maria Cristina Figueroa Magalhães; Marianne Rodrigues Fernandes; Ney Pereira Carneiro Dos Santos

doi:10.3390/jpm14050464

Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials

J Pers Med. 2024 Apr 27;14(5):464. doi: 10.3390/jpm14050464.

Affiliations

¹ Oncology Research Center, Federal University of Pará, Belem 66073-005, Brazil.
² School of Medicine, Federal University of Triângulo Mineiro, Uberaba 38025-180, Brazil.
³ School of Medicine, University of São Paulo, São Paulo 01246-903, Brazi.
⁴ School of Medicine, Federal University of Amazonas, Manaus 69080-900, Brazil.
⁵ School of Medicine, Catholic University of Minas Gerais, Belo Horizonte 32010-025, Brazil.
⁶ School of Medicine, Federal University of Santa Catarina, Florianópolis 88040-900, Brazil.
⁷ School of Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
⁸ Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
⁹ Mackenzie Evangelical University Hospital, Curitiba 80730-150, Brazil.

Abstract

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2-) early-stage breast cancer (esBC) is still to be confirmed.

Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant.

Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829).

Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2- esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.

Keywords: cancer; cyclin-dependent kinase 4/6 inhibitors; early-stage breast cancer; endocrine therapy.

Publication types

Review

Grants and funding

This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Pró-Reitoria de Pesquisa e Pós-Graduação da UFPA (PROPESP). We thank Federal University of Pará (UFPA) and the Center for Research in Oncology (NPO/UFPA). The design of the study, sample collection, data analysis, interpretation, and manuscript writing were conducted independently of any influence or involvement from the funding agencies.