Department of Medicine, Staten Island University Hospital, Staten Island, New York.
Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
Curr Probl Cancer. 2022 Jun;46(3):100859. doi: 10.1016/j.currproblcancer.2022.100859. Epub 2022 Mar 28.
CDK 4/6 inhibitors have been yielding propitious results when with hormone therapy in the management of Her2-negative and hormone-receptor (HR)-positive metastatic breast cancer, palbociclib being one of the first molecules investigated in this setting. However, the response to CDK4/6 inhibitors is variable. To identify predictive and prognostic factors of response to this therapeutic regimen. Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole. PFS was the primary endpoint in the evaluation of response to treatment. This survival was then further segregated according to various characteristics: histological (type, grade, hormone receptors), metastatic site, line of treatment, response type at initial assessment, and best response achieved. The data was then processed by two statistical analysis models: Kaplan-Meier and univariate preceding multivariate Cox proportional risks. Sixty patients were included and followed for a median follow-up duration of 15.98 months. PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033). Regarding the Hazard Ratio of progression, we note age (HR 0.941; P = 0.019), liver metastases (HR 2.751; P = 0.051), response at initial evaluation (HR<1; P < 0.001) and best response (HR<1; P = 0.003). PFS reached similar figures to those of international studies. The absence of progesterone receptors, presence of liver metastases, and use as second-line or beyond are associated with a reduced median PFS. One year age increase (protective factor), liver metastases (risk factor), response at initial evaluation, and best response achieved are identified as the most predictive factors of the response to this treatment regimen and of the progression risk.
CDK4/6 抑制剂与激素治疗联合用于管理 Her2 阴性和激素受体（HR）阳性转移性乳腺癌时取得了良好的效果，帕博西尼是该治疗方案中最早研究的分子之一。然而，对 CDK4/6 抑制剂的反应是可变的。为了确定对这种治疗方案的反应的预测和预后因素。符合条件的患者为接受来曲唑联合帕博西尼治疗的 HR+和 Her2-晚期乳腺癌女性。无孕激素受体患者的 PFS 中位数为 12.99 个月（vs 阳性雌激素和孕激素受体患者的 20.05 个月；P=0.046），存在肝转移患者的 PFS 中位数为 13.02 个月（vs 无肝转移患者的 22.98 个月；P=0.007），二线及以上患者的 PFS 中位数为 15.94 个月（vs 一线患者的 22.98 个月；P=0.033）。
关于进展的危险比，我们注意到年龄（HR 0.941；P=0.019）、肝转移（HR 2.751；P=0.051）、初始评估时的反应（HR<1；P < 0.001）和最佳反应（HR<1；P=0.003）。PFS 达到了与国际研究相似的水平。无孕激素受体、存在肝转移以及作为二线或以上治疗的患者的中位 PFS 降低。年龄增加一年（保护因素）、肝转移（危险因素）、初始评估时的反应和最佳反应是对该治疗方案的反应和进展风险的最具预测性的因素。
