Academic Trials Promoting Team, Institut Jules Bordet and l'Université Libre de Bruxelles (ULB), Brussels, Belgium; Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center - IRCCS, Humanitas Cancer Center, Rozzano, Milan; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele - Milan, Italy.
Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil.
ESMO Open. 2021 Apr;6(2):100091. doi: 10.1016/j.esmoop.2021.100091. Epub 2021 Mar 18.
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.
细胞周期蛋白依赖性激酶 4/6 抑制剂（CDK4/6is）与内分泌治疗（ET）联合是激素受体阳性（HR+）、HER2 阴性（HER2-）晚期乳腺癌（BC）患者的标准治疗方法。然而，迄今为止，评估辅助 CDK4/6is 的研究结果相互矛盾。
我们进行了系统评价和荟萃分析，以评估 HR+/HER2-早期乳腺癌（EBC）患者接受辅助 ET 加用 CDK4/6is 是否会影响生存结局和安全性。本研究根据系统评价和荟萃分析的首选报告项目（PRISMA）指南进行，并在 PROSPERO 数据库（ID：CRD42020218597）中进行了注册。对 PubMed、Cochrane 和 EMBASE 数据库以及主要会议记录进行了系统检索，检索时间截至 2020 年 12 月 15 日。纳入 HR+/HER2-EBC 患者接受 CDK4/6is 联合 ET 与单独 ET 辅助治疗的随机对照试验。使用随机效应模型计算生存和安全性结局的汇总风险比（HR）和优势比（OR）及其 95%置信区间（95%CI）。
来自三项研究（N=12647 例）的数据显示，辅助 ET 加用 CDK4/6is 治疗具有侵袭性无病生存（IDFS）获益的趋势（HR 0.85，95%CI 0.71-1.01；P=0.071）。未观察到远处无复发生存的显著改善（HR 0.83，95%CI 0.58-1.19；P=0.311）。与 ET 加用 CDK4/6is 相比，全级别的毒性和早期治疗中断的风险显著增加（OR 9.36，95%CI 3.46-25.33，P<0.001，OR 22.11，95%CI 9.45-51.69，P<0.001）。
HR+/HER2-EBC 患者接受辅助 CDK4/6is 治疗显示出 IDFS 获益的趋势，并且毒性和治疗中断的风险增加。辅助 CDK4/6is 的作用仍存在争议，需要对这些随机对照试验进行更长时间的随访，才能支持临床实践的直接改变。
