Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. Objective: The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2− BC. Method: We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. Results: Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 #x3c; 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81–13.03, p #x3c; 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39–34.58, p = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17–35.88, p #x3c; 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04–2.85, p = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59–29.61, p #x3c; 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41–20.11, p #x3c; 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29–0.87, p = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12–2.07, p = 0.342) and reduce the residual cancer burden (RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, p = 0.121; RCB 2–3: OR = 2.30, 95% CI = 0.89–5.91, p = 0.084). Conclusions: The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.
Oncol Res Treat

中文翻译：

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细胞周期蛋白依赖性激酶 4/6 抑制剂联合内分泌治疗 HR+/HER2− 乳腺癌的新辅助治疗：系统评价和荟萃分析

背景：细胞周期蛋白依赖性激酶 (CDK) 4/6 抑制剂已被提倡用于转移性激素受体 (HR)+/人表皮生长因子受体 2 (HER2)- 乳腺癌 (BC) 的辅助治疗。然而，在新辅助治疗中加入 CDK 4/6 抑制剂的有效性并非毫无疑问。目的：本研究的目的是评估新辅助 CDK 4/6 抑制剂 + 内分泌治疗 (ET) 与新辅助内分泌单药治疗或标准新辅助化疗在 HR+/HER2− BC 中的疗效和毒性。方法：我们在 PubMed、Cochrane 图书馆、Web of Science 和 Embase 在线数据库中搜索了 2021 年 4 月之前用英语编写的随机对照试验和单臂研究。结果：分析了将 CDK 4/6 抑制剂 + ET 作为新辅助治疗与单独 ET 进行比较的五项研究和将新辅助 CDK 4/6 抑制剂 + ET 与新辅助化疗进行比较的 2 项研究。新辅助 CDK 4/6 抑制剂 + ET 提高了完全细胞周期停滞率（CCCA：中央 Ki67 #x3c；2.7%，优势比 [OR] = 7.91，95% 置信区间 [CI] = 4.81–13.03，p #x3c ; 0.001)，增加了不良事件的风险（AE；尤其是≥3 AE；所有级别的 AE：OR = 9.10，95% CI = 2.39–34.58，p = 0.001；AE ≥3：OR = 12.24，95 % CI = 4.17–35.88, p #x3c; 0.001)，导致 BC 患者的病理完全反应 (pCR) 没有显着差异（OR = 0.34，95% CI = 0.04–2.85，p= 0.318) 与内分泌单一疗法相比。此外，亚组分析显示，3种CDK 4/6抑制剂均提高了CCCA的发生率（ribociclib：OR = 10.31, 95% CI = 3.59–29.61, p #x3c; 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40，p = 0.027，abemaciclib：OR = 8.28，95% CI = 3.41–20.11，p #x3c；0.001）。与新辅助化疗相比，新辅助 CDK 4/6 抑制剂加 ET 降低了 AE ≥3 的风险（OR = 0.50，95% CI = 0.29–0.87，p = 0.015），并显示出相似的达到 pCR 的能力（OR = 0.50, 95 % CI = 0.12–2.07, p = 0.342 ) 并减少残余癌症负担（RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, p= 0.121; RCB 2–3：OR = 2.30，95% CI = 0.89–5.91，p = 0.084）。结论：结果表明，与内分泌单药治疗相比，联合治疗具有更高的疗效和毒性，并且显示出与新辅助化疗相似的疗效和更好的安全性。
肿瘤资源治疗