周期蛋白依赖性激酶4/6抑制剂在激素受体阳性、her2阴性的晚期乳腺癌中的进展：一项系统回顾和荟萃分析（REIGNITE研究）。

IF 8.3 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-10-01 DOI:10.1016/j.esmoop.2025.105808

L.F.C. de Almeida , L.F. Leite , V.O.C. Filho , M.M. Noronha , A.P. Cappellaro , M. Gouveia , J.L. da Silva , B. Ernst , A.C. de Melo , P. Tarantino , F. Batalini

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引用次数: 0

摘要

背景：在内分泌治疗（ET）中加入细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）被认为是晚期hr阳性/ her2阴性乳腺癌的一线治疗方法。然而，随着最近一些额外的靶向药物的批准，最佳的治疗序列仍然不确定，也不清楚CDK4/6i的益处是否会超出一线治疗的进展。材料和方法：我们进行了一项系统回顾和荟萃分析，以评估CDK4/6i在一线治疗进展后在二线治疗中的疗效，特别关注PIK3CA或ESR1突变的患者。我们纳入了随机临床试验（rct），比较CDK4/6i联合ET和单独ET在一线治疗CDK4/6i后肿瘤进展的患者。使用95%置信区间（CI）的随机效应模型对结果进行汇总。结果：纳入5项随机对照试验，共1184例患者。总体而言，CDK4/6i联合ET与单独ET相比显著改善了无进展生存期（PFS），风险比为0.73 (95% CI 0.56-0.94, P < 0.05)，切换CDK4/6i的患者获益更显著（风险比0.61,95% CI 0.48-0.77, P < 0.05）。PIK3CA体细胞突变（风险比0.71,95% CI 0.52-0.98, P < 0.05）和ESR1突变（风险比0.66,95% CI 0.49-0.89, P < 0.05）患者获益一致。毒性特征与CDK4/6i已知的副作用一致。结论：我们的研究结果支持在二线环境中切换CDK4/6i的策略，并且即使在PIK3CA或ESR1突变患者中也显示出持续的益处。

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Cyclin-dependent kinase 4/6 inhibitors beyond progression in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis (REIGNITE study)

Background

Adding cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy (ET) is considered the first-line treatment of advanced HR-positive/HER2-negative breast cancer. However, with the recent approval of several additional targeted agents, the optimal treatment sequencing remains uncertain, and it is unclear whether the benefits of CDK4/6i extend beyond progression on first-line therapy.

Materials and methods

We conducted a systematic review and meta-analysis to evaluate the efficacy of CDK4/6i in the second-line setting after progression on CDK4/6i in the first line, with a particular focus on patients who had either PIK3CA or ESR1 mutation. We included randomized clinical trials (RCTs) comparing CDK4/6i combined with ET to ET alone in patients who experienced tumor progression on CDK4/6i treatment in the first-line setting. The results were pooled using a random-effects model with 95% confidence interval (CI).

Results

Five RCTs encompassing 1184 patients were included. Overall, CDK4/6i plus ET significantly improved progression-free survival (PFS) versus ET alone, yielding a hazard ratio of 0.73 (95% CI 0.56-0.94, P < 0.05), with a more prominent benefit in patients who switched the CDK4/6i (hazard ratio 0.61, 95% CI 0.48-0.77, P < 0.05). The benefit was consistent in patients with somatic PIK3CA mutations (hazard ratio 0.71, 95% CI 0.52-0.98, P < 0.05), and ESR1 mutations (hazard ratio 0.66, 95% CI 0.49-0.89, P < 0.05). The toxicity profile was compatible with the known side effects from CDK4/6i.

Conclusions

Our results support the strategy of switching the CDK4/6i in the second-line setting and demonstrate persistent benefit even in patients with PIK3CA or ESR1 mutations.

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.