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

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...

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Bibliographic Details
Published in:ESMO open 2021-04, Vol.6 (2), p.100091-100091, Article 100091
Main Authors: Agostinetto, E., Vian, L., Caparica, R., Bruzzone, M., Ceppi, M., Lambertini, M., Pondé, N., de Azambuja, E.
Format: Article
Language:English
Subjects:
adjuvant
breast cancer
Breast Neoplasms - drug therapy
CDK4/6 inhibitors
Cyclin-Dependent Kinase 4 - antagonists & inhibitors
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
endocrine therapy
Female
Hormones
HR-positive
Humans
Neoplasm Recurrence, Local
Receptor, ErbB-2 - genetics
Receptors, Estrogen
Review
survival
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Summary: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. 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. 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). 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. •Studies evaluating CDK4/6is in the adjuvant setting provided contradictory results thus far.•In our meta-analysis, adjuvant CDK4/6is showed a trend for IDFS benefit.•No significant improvement in DRFS was observed.•Adjuvant CDK4/6is were associated with an increased risk of toxicities and treatment discontinuation.•The role of adjuvant CDK4/6is remains controversial, and a longer follow-up is needed.
ISSN:2059-7029
2059-7029
DOI:10.1016/j.esmoop.2021.100091