Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Cancer Biol Med. 2024 Sep 11;21(10):934-50. doi: 10.20892/j.issn.2095-3941.2024.0204.
CDK4/6 inhibitors (CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor (HR)-positive advanced breast cancer (ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2 (HER2)- ABC.
This retrospective study enrolled 82 patients with HR+/HER2- ABC who were treated with cross-line CDK4/6is (abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progression-free survival (PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human Services.
Eighty-two HR+/HER2- ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months (95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were observed.
Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2- ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.
CDK4/6 抑制剂（CDK4/6is）与内分泌治疗联合应用，已在激素受体（HR）阳性晚期乳腺癌（ABC）的治疗中确立了核心地位，并改变了治疗格局。在先前 CDK4/6i 进展后继续使用另一种 CDK4/6i 的跨线 CDK4/6i 治疗仍可能提供有利的治疗效果。跨线 CDK4/6i 治疗是目前正在进行的提高 HR+/人表皮生长因子受体 2（HER2）-ABC 患者治疗效果的研究领域之一。
本回顾性研究纳入了 82 例 HR+/HER2-ABC 患者，这些患者在先前 CDK4/6i 进展后接受了跨线 CDK4/6i（阿贝西利、哌柏西利、瑞博西利和达尔西利）治疗。主要终点为根据实体瘤反应评价标准 1.1 版评估的无进展生存期（PFS）。次要终点包括毒性、客观缓解率、疾病控制率和总生存期。不良事件（AE）根据美国卫生与公众服务部发布的不良事件通用术语标准 5.0 版进行分级。
2022 年 1 月至 2024 年 2 月，共纳入 82 例接受跨线 CDK4/6i 治疗的 HR+/HER2-ABC 患者。患者的中位年龄为 60 岁。所有患者的中位 PFS 为 7.6 个月（95%CI，5.9-9.2）。Cox 回归分析确定肺转移和在接受先前 CDK4/6i 治疗后转为内分泌治疗是 PFS 的独立预测因素。值得注意的是，先前接受阿贝西利治疗并在疾病进展后转为哌柏西利的患者中位 PFS 为 10.7 个月。在先前 CDK4/6i 进展后转为化疗，然后转为后续 CDK4/6i 的策略值得进一步研究。血液学毒性是最常见的≥3 级 AE。未观察到致命的安全事件。
跨线 CDK4/6i 治疗在 HR+/HER2-ABC 患者中具有显著的临床获益和可管理的安全性，这突显了跨线 CDK4/6i 治疗作为一种有效治疗策略的潜力。
