Systematic review and meta-analysis of post-progression outcomes in ER+/HER2− metastatic breast cancer after CDK4/6 inhibitors within randomized clinical trials

ESMO Open

article

E. Munzone¹  E. Pagan²  V. Bagnardi²  E. Montagna¹  G. Cancello¹  S. Dellapasqua¹  M. Iorfida¹  M. Mazza¹  M. Colleoni¹ 

[1] Division of Medical Senology, European Institute of Oncology;Department of Statistics and Quantitative Methods, University of Milan-Bicocca;Program of Breast Health European Institute of Oncology

关键词: metastatic breast cancer;    ER-positive/HER2-negative;    endocrine therapy;    CDK4/6 inhibitors;    PFS2;    TTC;   

DOI  :  10.1016/j.esmoop.2021.100332

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy (ET) deeply transformed the treatment landscape of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. Randomized clinical trials suggest that second progression-free survival (PFS2) was not compromised and time to subsequent chemotherapy (TTC) may be delayed. We carried out a meta-analysis to assess the benefit on PFS2 and on delaying the TTC.Methods We conducted a systematic literature search of randomized clinical trials with CDK4/6 inhibitors and ET reporting PFS2 or TTC of HR+/HER2− pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC using random-effects models with 95% confidence intervals (CI). I2 was used to quantify heterogeneity between results of the studies.Results Eight studies (MONALEESA-2/3/7, MONARCH-2/3, PALOMA-1/2/3) were included in this analysis (N = 4580 patients). PFS2 benefit was observed in patients who received CDK4/6 inhibitors plus ET (pooled HR = 0.68, 95% CI = 0.62-0.74, I2 = 0%) and also a delay in subsequent TTC (pooled HR = 0.65, 95% CI = 0.60-0.71, I2 = 0%). A benefit in terms of PFS (pooled HR = 0.55, 95% CI = 0.51-0.59, I2 = 0%) and overall survival (pooled HR = 0.76, 95% CI = 0.69-0.84, I2 = 0%) was also observed.Conclusions CDK4/6 inhibitors plus ET compared with ET alone improve PFS2 and TTC. The delay of chemotherapy may postpone the start of a more toxic treatment option, delaying related toxicities and potentially maintaining a better quality of life for patients, for a longer time. The benefit in PFS2 may postpone the onset of endocrine resistance and help further validate this treatment approach.

【 授权许可】

CC BY|CC BY-NC-ND