Department of Oncology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8000, Aarhus N, Denmark.
Department of Oncology, University Hospital Copenhagen, Copenhagen, Denmark.
Breast Cancer Res Treat. 2021 Aug;188(3):799-809. doi: 10.1007/s10549-021-06215-6. Epub 2021 Apr 10.
Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2-) metastatic breast cancer (MBC) has improved with the approval of CDK 4/6 inhibitors. Clinical trials with the CDK4/6 inhibitor ribociclib, suggest that 35% to 57.5% of the patients require a dose reduction during ribociclib treatment. Data on the possible consequences of dose reduction concerning efficacy is needed.
A retrospective cohort study on patients with ER+ HER2- MBC from three Danish oncology departments. Data on tolerability and progression-free survival were collected from electronic health records.
One hundred and twenty-eight patients with ER+ HER2- MBC who initiated ribociclib treatment between 1st of January 2018 to 31st of March 2020 were included in our analysis. Of these patients, 48.4% required one or more dose reductions. Overall median PFS was 19.2 months (CI-95% 14.3-NR). Patients with one or more dose reductions did not have decreased median PFS (19.2 months, CI-95% 14.3-NR compared to 12.2 months, CI-95% 7.3-NR, p = 0.078). Frequency of adverse events were as previously reported, with grade III and IV neutropenia occurring in 45.3% and 7% of patients, respectively. Patients treated with fulvestrant versus an aromatase inhibitor and patients with lymph node involvement at baseline had lower odds of requiring a dose reduction (OR = 0.30, CI-95% 0.12-0.73 & OR = 0.41, CI-95% 0.18-0.89, respectively).
Our results indicate that dose reduction of ribociclib is safe and do not compromise the efficacy of the treatment. Furthermore, the study supports translation of results from the MONALEESA trials to patients treated in real-world clinical settings.
随着 CDK4/6 抑制剂的批准，治疗雌激素受体阳性（ER+）、人表皮生长因子受体 2 阴性（HER2-）转移性乳腺癌（MBC）的方法得到了改善。CDK4/6 抑制剂瑞博西利的临床试验表明，35%至 57.5%的患者在瑞博西利治疗期间需要减少剂量。需要有关减少剂量对疗效可能产生的后果的数据。
这是一项来自丹麦三个肿瘤学部门的 ER+HER2-MBC 患者的回顾性队列研究。从电子病历中收集了耐受性和无进展生存期的数据。
本研究共纳入了 128 例于 2018 年 1 月 1 日至 2020 年 3 月 31 日期间开始接受瑞博西利治疗的 ER+HER2-MBC 患者。其中，48.4%的患者需要进行一次或多次剂量减少。总体中位无进展生存期为 19.2 个月（95%CI-95%无进展生存期-NR）。发生一次或多次剂量减少的患者中位无进展生存期无显著差异（19.2 个月，95%CI-95%无进展生存期-NR 与 12.2 个月，95%CI-95%无进展生存期-NR，p=0.078）。不良反应的频率与之前报道的相似，分别有 45.3%和 7%的患者发生了 3 级和 4 级中性粒细胞减少症。与接受芳香化酶抑制剂治疗的患者相比，接受氟维司群治疗的患者以及基线时淋巴结受累的患者需要减少剂量的可能性较低（OR=0.30，95%CI-95%0.12-0.73 和 OR=0.41，95%CI-95%0.18-0.89）。
我们的结果表明，瑞博西利的剂量减少是安全的，不会影响治疗的疗效。此外，该研究支持将 MONALEESA 试验的结果转化为在真实临床环境中治疗的患者。
