Department of General Surgery, Yichun People's Hospital, No. 1061 Jinxiu Avenue, Yiyang New District, Yichun, jiangxi, 336000, China.
BMC Cancer. 2024 Aug 21;24(1):1031. doi: 10.1186/s12885-024-12782-w.
Does incorporating Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into endocrine therapy (ET) effectively enhance survival outcomes, notably overall survival (OS), among individuals with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer? This remains a clinical controversy. We compared the antitumor efficacy and adverse effects (AEs) between CDK4/6 inhibitors + ET (CET) and placebo + ET (PET) by conducting a phase III randomized controlled trials (RCTs) based meta-analysis.
Seven databases were searched to identify eligible studies, comprising Phase III RCTs comparing CET to PET. The primary endpoints were OS and progression-free survival (PFS), with secondary endpoints including responses and adverse events (AEs).
Seven RCTs (DAWNA-2, MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH-3, PALOMA-2, and PALOMA-4) were included. The CET group exhibited significantly improved OS (HR: 0.81 [0.74, 0.88]), PFS (HR: 0.57 [0.52, 0.63]), objective response rate (RR: 1.31 [1.20, 1.43]), and clinical benefit rate (RR: 1.11 [1.07, 1.15]). These benefits were consistent across almost all subgroups. Additionally, the CET group showed better overall survival rates (OSR) from 24 to 60 months (OSR 24-60 m) and progression-free survival rates (PFSR) from 6 to 60 months (PFSR 6-60 m). However, more total AEs, grade 3-5 AEs, and serious AEs were found in CET group. The top 5 grade 3-5 AEs in the CET group were neutropenia (59.39%), leukopenia (24.11%), decreased white blood cell count (12.99%), hypertension (7.03%), and increased alanine aminotransferase (5.91%).
The superiority of CET over PET in HR+/HER2- advanced breast cancer is evident, showing improved survival and responses. Nonetheless, the higher incidence of AEs, specifically hematologic AEs, requires cautious attention.
在激素受体阳性（HR+）、人表皮生长因子受体 2 阴性（HER2-）晚期乳腺癌患者中，将细胞周期蛋白依赖性激酶 4/6（CDK4/6）抑制剂与内分泌治疗（ET）联合使用是否能有效提高生存结局，尤其是总生存（OS），这仍然存在临床争议。我们通过开展 III 期随机对照试验（RCT）的荟萃分析，比较了 CDK4/6 抑制剂+ET（CET）与安慰剂+ET（PET）的抗肿瘤疗效和不良反应（AEs）。
我们在七个数据库中检索了符合条件的研究，包括比较 CET 与 PET 的 III 期 RCT。主要终点是 OS 和无进展生存期（PFS），次要终点包括反应和不良反应（AEs）。
纳入了 7 项 RCT（DAWNA-2、MONALEESA-2、MONALEESA-3、MONALEESA-7、MONARCH-3、PALOMA-2 和 PALOMA-4）。CET 组 OS（HR：0.81 [0.74，0.88]）、PFS（HR：0.57 [0.52，0.63]）、客观缓解率（RR：1.31 [1.20，1.43]）和临床获益率（RR：1.11 [1.07，1.15]）均显著改善。这些获益在几乎所有亚组中均一致。此外，CET 组在 24 至 60 个月的总生存率（OSR 24-60 m）和 6 至 60 个月的无进展生存率（PFSR 6-60 m）方面表现更好。然而，CET 组出现更多的总不良反应（AEs）、3-5 级 AEs 和严重 AEs。CET 组的前 5 大 3-5 级 AEs 是中性粒细胞减少症（59.39%）、白细胞减少症（24.11%）、白细胞计数减少（12.99%）、高血压（7.03%）和丙氨酸氨基转移酶升高（5.91%）。
在 HR+/HER2-晚期乳腺癌中，CET 优于 PET，表现为生存和反应改善。然而，更高的不良反应发生率，特别是血液学不良反应，需要谨慎关注。
