细胞周期蛋白依赖性激酶 4 和 6 抑制剂联合新辅助内分泌治疗雌激素受体阳性早期乳腺癌：系统评价和荟萃分析。
Cyclin-dependent kinase 4 and 6 inhibitors in combination with neoadjuvant endocrine therapy in estrogen receptor-positive early breast cancer: a systematic review and meta-analysis.
机构信息
Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China.
出版信息
Clin Exp Med. 2023 Jun;23(2):245-254. doi: 10.1007/s10238-022-00814-3. Epub 2022 Mar 19.
The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42-14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59-2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13-4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21-2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47-2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76-202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02-115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC.
CDK4/6 抑制剂联合内分泌治疗使雌激素受体阳性/人表皮生长因子受体 2 阴性（ER+/HER2-）转移性乳腺癌患者受益；然而，其在 ER+/HER2-早期乳腺癌（EBC）新辅助治疗中的效果尚不清楚。截至 2021 年 1 月 30 日，我们在 PubMed、Embase、Cochrane 图书馆和主要肿瘤学会议上系统地检索了 CDK4/6 抑制剂联合新辅助内分泌治疗（NET）与 NET/新辅助化疗（NACT）单独治疗的试验。我们评估了 CDK4/6 抑制剂联合 NET 与 NET/NACT 单独治疗 ER+/HER2-EBC 的疗效。使用了 6 项包括 803 例接受 CDK4/6 抑制剂联合 NET 治疗与 NET/NACT 单独治疗的患者的研究。与 NET/NACT 单独治疗相比，CDK4/6 抑制剂联合 NET 增加了完全细胞周期停滞（CCCA）率（OR，9.00；95%CI，5.42-14.96；P<0.001）。CDK4/6 抑制剂联合 NET 与 NET/NACT 单独治疗在术前内分泌预后指数（PEPI）-0 率（OR，1.13；95%CI，0.59-2.18；P=0.71）、病理完全缓解（pCR）率（OR，0.75；95%CI，0.13-4.29；P=0.74）、客观缓解率（ORR）（OR，0.70；95%CI，0.21-2.29；P=0.55）和疾病控制率（DCR）（OR，1.16；95%CI，0.47-2.89；P=0.74）方面无显著差异。CDK4/6 抑制剂联合 NET 预示着中性粒细胞减少症（OR，56.43；95%CI，15.76-202.11；P<0.001）作为一种不良反应（AE）和丙氨酸氨基转移酶（ALT）水平升高（OR，15.30；95%CI，2.02-115.98；P=0.008）作为 3/4 级 AE 的风险较高。与 NET/NACT 单独治疗相比，CDK4/6 抑制剂联合 NET 增加了 ER+/HER2-EBC 患者的 CCCA 率。CDK4/6 抑制剂联合 NET 并未显著提高 PEPI-0 率、pCR 率、ORR 或 DCR。该联合增加了中性粒细胞减少症和 ALT 水平升高的风险。在新辅助治疗中，CDK4/6 抑制剂联合 NET 可能是治疗 ER+/HER2-EBC 的一种选择。
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