PDF(Pubmed)
Abstract：
BACKGROUND: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored.
METHODS: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC.
RESULTS: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients\' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment.
CONCLUSIONS: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.
METHODS: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC.
RESULTS: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients\' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment.
CONCLUSIONS: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.
摘要：
背景：乳腺癌（BC）发病率随年龄增长而增加，特别是在HR阳性/HER2阴性亚型中。细胞周期蛋白依赖性激酶4和6抑制剂（CDK4/6is）以及内分泌治疗（ET）已成为HR阳性/HER2阴性晚期和早期BC的有希望的治疗方法。然而,其功效,安全,对老年和体弱患者的生活质量（QoL）的影响仍未得到充分探索。
方法：本立场文件评估了2015年至2024年的现有文献，重点研究了65岁及以上HR阳性/HER2阴性BC患者的CDK4/6使用情况。
结果：我们的分析有条不紊地解决了老年BC患者人群中CDK4/6is利用的关键问题，从转移和辅助设置组织发现。在转移性环境中，CDK4/6显着改善无进展生存期（PFS），在年轻患者中观察到的平行益处，并建议潜在的总体生存（OS）益处，保证进一步调查。尽管≥3级不良事件（AE）的发生率增加，如中性粒细胞减少症和虚弱症，与传统化疗相比，CDK4/6的毒性明显较低，具有可控的副作用。QoL分析表明，将CDK4/6is整合到治疗方案中不会显着影响老年BC患者的日常生活和症状管理。特别注意脆弱的亚组，建议采用个性化方法来平衡疗效和不良反应，例如，在疾病负担低的患者中，仅从ET开始并在进展时引入CDK4/6。过渡到佐剂设置，早期结果,特别是abemaciclib，表明对无病生存率（DFS）的积极影响，强调需要继续分析以验证这些发现并评估长期影响。然而,关于老年患者的数据不足以断定他们是否真正从这种治疗中获益.
结论：总体而言，CDK4/6在老年BC患者中具有良好的获益-风险特征，至少在公元前晚期；然而，需要进一步的研究来优化治疗策略并改善该人群的结局.
方法：本立场文件评估了2015年至2024年的现有文献，重点研究了65岁及以上HR阳性/HER2阴性BC患者的CDK4/6使用情况。
结果：我们的分析有条不紊地解决了老年BC患者人群中CDK4/6is利用的关键问题，从转移和辅助设置组织发现。在转移性环境中，CDK4/6显着改善无进展生存期（PFS），在年轻患者中观察到的平行益处，并建议潜在的总体生存（OS）益处，保证进一步调查。尽管≥3级不良事件（AE）的发生率增加，如中性粒细胞减少症和虚弱症，与传统化疗相比，CDK4/6的毒性明显较低，具有可控的副作用。QoL分析表明，将CDK4/6is整合到治疗方案中不会显着影响老年BC患者的日常生活和症状管理。特别注意脆弱的亚组，建议采用个性化方法来平衡疗效和不良反应，例如，在疾病负担低的患者中，仅从ET开始并在进展时引入CDK4/6。过渡到佐剂设置，早期结果,特别是abemaciclib，表明对无病生存率（DFS）的积极影响，强调需要继续分析以验证这些发现并评估长期影响。然而,关于老年患者的数据不足以断定他们是否真正从这种治疗中获益.
结论：总体而言，CDK4/6在老年BC患者中具有良好的获益-风险特征，至少在公元前晚期；然而，需要进一步的研究来优化治疗策略并改善该人群的结局.
