CDK4 & 6 inhibitors have enhanced the effectiveness of endocrine therapy (ET) in patients with advanced breast cancer (ABC). This paper presents exploratory analyses examining patient and disease characteristics that may inform in whom and when abemaciclib should be initiated. MONARCH 2 and 3 enrolled women with HR+, HER2- ABC. In MONARCH 2, patients whose disease had progressed while receiving ET were administered fulvestrant+abemaciclib/placebo. In MONARCH 3, patients received a nonsteroidal aromatase inhibitor+abemaciclib/placebo as initial therapy for advanced disease. A combined analysis of the two studies was performed to determine significant prognostic factors. Efficacy results (PFS and ORR in patients with measurable disease) were examined for patient subgroups corresponding to each significant prognostic factor. Analysis of clinical factors confirmed the following to have prognostic value: bone-only disease, liver metastases, tumor grade, progesterone receptor status, performance status, treatment-free interval (TFI) from the end of adjuvant ET, and time from diagnosis to recurrence. Prognosis was poorer in patients with liver metastases, progesterone receptor-negative tumors, high grade tumors, or short TFI (<36 months). Benefit (PFS hazard ratio, ORR increase) from abemaciclib was observed in all patient subgroups. Patients with indicators of poor prognosis had the largest benefit from the addition of abemaciclib. However, in MONARCH 3, for patients with certain good prognostic factors (TFI ≥ 36 months, bone-only disease) ET achieved a median PFS of >20 months. These analyses identified prognostic factors and demonstrated that patients with poor prognostic factors derived the largest benefit from the addition of abemaciclib.

CDK4和6抑制剂增强了晚期乳腺癌（ABC）患者的内分泌治疗（ET）的有效性。本文提供了探索性分析，检查了患者和疾病的特征，这些信息可以告知谁应在何时何地启动abemaciclib。MONARCH 2和3招募了具有HR +，HER2- ABC的女性。在MONARCH 2中，接受ET治疗期间病情恶化的患者接受了氟维司群+ abemaciclib /安慰剂治疗。在MONARCH 3中，患者接受非甾体芳香酶抑制剂+ abemaciclib /安慰剂作为晚期疾病的初始治疗。对两项研究进行了综合分析，以确定重要的预后因素。检查与每个重要预后因素相对应的患者亚组的疗效结果（可测量疾病患者的PFS和ORR）。临床因素分析证实以下各项具有预后价值：仅骨疾病，肝转移，肿瘤等级，孕激素受体状态，性能状态，从佐剂ET结束起的无治疗间隔时间（TFI），以及从诊断到复发的时间。肝转移，孕激素受体阴性肿瘤，高级别肿瘤或短暂TFI（<36个月）的患者的预后较差。在所有患者亚组中均观察到了abemaciclib的益处（PFS危险比，ORR增加）。预后较差的患者受益于abemaciclib的最大获益。但是，在MONARCH 3中，对于具有某些良好预后因素（TFI≥36个月，仅骨病）的患者，ET的中位PFS大于20个月。