CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

ESMO Open

article

E. Agostinetto¹  L. Vian⁴  R. Caparica¹  M. Bruzzone⁵  M. Ceppi⁵  M. Lambertini⁶  N. Pondé⁴  E. de Azambuja¹ 

[1] Academic Trials Promoting Team, Institut Jules Bordet and l"Université Libre de Bruxelles;Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center – IRCCS, Humanitas Cancer Center;Department of Biomedical Sciences, Humanitas University;Clinical Oncology Department, AC Camargo Cancer Center;Unit of Clinical Epidemiology, IRCCS Ospedale Policlinico San Martino;Department of Internal Medicine and Medical Specialties ,(DiMI), School of Medicine, University of Genova;Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino

关键词: breast cancer;    HR-positive;    adjuvant;    CDK4/6 inhibitors;    endocrine therapy;    survival;   

DOI  :  10.1016/j.esmoop.2021.100091

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The combination of cyclin-dependent kinases 4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is standard of care for patients with hormone receptor-positive (HR+), HER2-negative (HER2−) advanced breast cancer (BC). However, studies evaluating adjuvant CDK4/6is provided contradictory results thus far.Materials and methods We conducted a systematic review and meta-analysis to assess if the addition of CDK4/6is to adjuvant ET impacts on survival's outcomes and safety of patients with HR+/HER2− early BC (EBC). This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and was registered in the PROSPERO database (ID: CRD42020218597). A systematic review of PubMed, Cochrane and EMBASE databases and major conference proceedings was performed up to 15 December 2020. All randomized controlled trials including patients with HR+/HER2− EBC treated with CDK4/6is plus ET versus ET alone in the adjuvant setting were included. Pooled hazard ratios (HRs) and odds ratios (ORs) for survival and safety outcomes, respectively, were calculated with 95% confidence intervals (95% CIs) using random effect models.Results With data available from three studies (N = 12 647), the addition of CDK4/6is to adjuvant ET showed a trend for a benefit in terms of invasive disease-free survival (IDFS; HR 0.85, 95% CI 0.71-1.01; P = 0.071). No significant improvement in distant relapse-free survival was observed (HR 0.83, 95% CI 0.58-1.19; P = 0.311). The risk of all-grade toxicities and early treatment discontinuation increased significantly with the addition of CDK4/6is to ET (OR 9.36, 95% CI 3.46-25.33, P < 0.001, and OR 22.11, 95% CI 9.45-51.69, P < 0.001, respectively).Conclusion The administration of adjuvant CDK4/6is to patients with HR+/HER2− EBC showed a trend for an IDFS benefit and an increase in the risk of toxicities and treatment discontinuation. The role of adjuvant CDK4/6is remains controversial and a longer follow-up of these randomized controlled trials is needed before supporting a straightforward change in clinical practice.

【 授权许可】

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