Ravani Lis Victoria, Calomeni Pedro, Vilbert Maysa, Madeira Thiago, Wang Ming, Deng Daxuan, Testa Laura, Colombo Bonadio Renata, Clifton Katherine, Wander Seth A, Lustberg Maryam
University of Sao Paulo Medical School, São Paulo, Brazil.
Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA.
JCO Oncol Pract. 2025 Jun;21(6):832-842. doi: 10.1200/OP-24-00649. Epub 2024 Dec 17.
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) combined with endocrine therapy (ET) are the standard of care in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (aBC). Yet, disease progression remains common. In the absence of established postprogression sequencing guidelines, we conducted a pooled analysis of Kaplan-Meier (KM)-derived patient data to assess the efficacy of subsequent treatment options after disease progression on CDK4/6i therapy.
We conducted a systematic review and meta-analysis searching PubMed, Embase, Cochrane, and conference proceedings for randomized trials and cohort studies published from 2016 to December, 2023. Studies assessing subsequent treatment postprogression on CDK4/6i in patients with HR+ HER2- aBC were included. We performed a pooled analysis of KM-derived individual patient data. Outcomes of interest were progression-free survival (PFS) and overall survival (OS). This study is registered in PROSPERO, CRD42023491090.
Of 12,895 identified records, 18 studies comprising 4,899 patients were included. Maintaining treatment with a CDK4/6i plus ET post-CDK4/6i progression was associated with longer PFS (hazard ratio [HR], 0.61 [95% CI, 0.53 to 0.70]; < .01) and prolonged OS (HR, 0.68 [95% CI, 0.60 to 0.77]; < .01) compared with ET monotherapy. The PFS benefit was seen in both continuing the previous CDK4/6i (HR, 0.67 [95% CI, 0.56 to 0.79]; < .01) and switching to a different CDK4/6i (HR, 0.68 [95% CI, 0.54 to 0.85]; < .01). Subsequent therapy with everolimus plus ET achieved similar PFS (HR, 1.10 [95% CI, 0.90 to 1.35]; = .35) and significantly shorter OS (HR, 1.52; [95% CI, 1.21 to 1.90], < .01) as compared with ET monotherapy.
This extensive data pool suggests significant benefit of CDK4/6i regimens after disease progression as compared with ET monotherapy. Our data also support current guideline recommendations of ET-based therapies over chemotherapy for treatment sequencing.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）联合内分泌治疗（ET）是激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）晚期乳腺癌（aBC）的标准治疗方案。然而，疾病进展仍然很常见。在缺乏既定的疾病进展后测序指南的情况下，我们对来自卡普兰-迈耶（KM）法得出的患者数据进行了汇总分析，以评估CDK4/6i治疗疾病进展后后续治疗方案的疗效。
我们进行了一项系统评价和荟萃分析，在PubMed、Embase、Cochrane以及会议论文集中检索2016年至2023年12月发表的随机试验和队列研究。纳入评估HR+ HER2- aBC患者CDK4/6i治疗疾病进展后后续治疗的研究。我们对来自KM法得出的个体患者数据进行了汇总分析。感兴趣的结局是无进展生存期（PFS）和总生存期（OS）。本研究已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42023491090。
在12895条检索到的记录中，纳入了18项研究，共4899例患者。与ET单药治疗相比，CDK4/6i进展后继续使用CDK4/6i加ET进行治疗与更长的PFS（风险比[HR]，0.61[95%置信区间，0.53至0.70]；P<0.01）和更长的OS（HR，0.68[95%置信区间，0.60至0.77]；P<0.01）相关。继续使用之前的CDK4/6i（HR，0.67[95%置信区间，0.56至0.79]；P<0.01）和换用不同的CDK4/6i（HR，0.68[95%置信区间，0.54至0.85]；P<0.01）均观察到PFS获益。与ET单药治疗相比，依维莫司加ET的后续治疗获得了相似的PFS（HR，1.10[95%置信区间，0.90至1.35]；P=0.35），但OS显著缩短（HR，1.52；[95%置信区间，1.21至1.90]，P<0.01）。
这个庞大的数据集表明，与ET单药治疗相比，疾病进展后CDK4/6i方案有显著益处。我们的数据也支持当前指南推荐的基于ET的治疗优于化疗用于治疗排序。
