PDF(Pubmed)
Abstract：
UNASSIGNED: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression.
UNASSIGNED: We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.
UNASSIGNED: Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment.
UNASSIGNED: Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.
UNASSIGNED: We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone.
UNASSIGNED: Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment.
UNASSIGNED: Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.
摘要：
■细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）代表激素受体阳性人表皮生长因子受体2（HER-2）阴性晚期乳腺癌的金标准。然而,疾病进展后的最佳治疗是一个有争议的问题。我们旨在评估CDK4/6i进展后与治疗结果相关的预测和预后因素。
■我们回顾性分析了2018年至2024年间CDK4/6i治疗进展的患者。基于分子结果的治疗（PIK3CA突变），遗传发现（BRCA1/2种系突变），或适应再活检中肿瘤表型的变化(向HER-2阳性疾病转化中的抗HER2治疗)被分组为定制治疗,并与基于内分泌的治疗和单独的化疗进行比较.
■用CDK4/6i治疗了512例患者。200名疾病进展患者被纳入研究。对CDK4/6i的反应持续时间不能预测对后续治疗的反应，而中枢神经系统的进展是最差的预后因素。30例患者没有资格接受后续治疗。CDK4/6i进展后的生存期在符合定制治疗条件的患者中显著延长。定制治疗患者（n=19）的中位PFS为13.5个月，而不是非定制治疗患者4.9个月（n=151；p=0.045）。定制治疗的12个月PFS为54.1%[95%CI24.1-76.7%]，而非定制治疗的PFS为18.5%[95%CI11.6-26.6%]。与使用非定制治疗的11.5个月相比，使用定制方法治疗的患者的中位OS未达到（p=0.016）。采用定制治疗的患者的24个月OS为80.2%[95%CI40.3-94.8%]，而采用非定制治疗的患者为21.1%[95%CI12.2-31.7%]。
■定制后续治疗策略似乎对于实现长期受益至关重要。需要进一步的研究，由于CDK4/6i进展后的预后仍然不佳，尤其是在影响中枢神经系统的情况下。
■我们回顾性分析了2018年至2024年间CDK4/6i治疗进展的患者。基于分子结果的治疗（PIK3CA突变），遗传发现（BRCA1/2种系突变），或适应再活检中肿瘤表型的变化(向HER-2阳性疾病转化中的抗HER2治疗)被分组为定制治疗,并与基于内分泌的治疗和单独的化疗进行比较.
■用CDK4/6i治疗了512例患者。200名疾病进展患者被纳入研究。对CDK4/6i的反应持续时间不能预测对后续治疗的反应，而中枢神经系统的进展是最差的预后因素。30例患者没有资格接受后续治疗。CDK4/6i进展后的生存期在符合定制治疗条件的患者中显著延长。定制治疗患者（n=19）的中位PFS为13.5个月，而不是非定制治疗患者4.9个月（n=151；p=0.045）。定制治疗的12个月PFS为54.1%[95%CI24.1-76.7%]，而非定制治疗的PFS为18.5%[95%CI11.6-26.6%]。与使用非定制治疗的11.5个月相比，使用定制方法治疗的患者的中位OS未达到（p=0.016）。采用定制治疗的患者的24个月OS为80.2%[95%CI40.3-94.8%]，而采用非定制治疗的患者为21.1%[95%CI12.2-31.7%]。
■定制后续治疗策略似乎对于实现长期受益至关重要。需要进一步的研究，由于CDK4/6i进展后的预后仍然不佳，尤其是在影响中枢神经系统的情况下。
