Provenzano L, Dieci M V, Curigliano G, Giuliano M, Botticelli A, Lambertini M, Rizzo G, Pedersini R, Sirico M, La Verde N, Gennari A, Zambelli A, Toss A, Piras M, Giordano M, Tagliaferri B, Generali D, Sartori D, Miliziano D, Menichetti A, Ligorio F, Zurlo C, Griguolo G, Berton Giachetti P P, Faso V, Corti C, Chiappe E, Scagnoli S, Pisegna S, Capasso C, De Angelis C, Arpino G, Criscitiello C, Guarneri V, Pruneri G, Mariani L, Vernieri C
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; IFOM ETS, AIRC Institute of Molecular Oncology, Milan, Italy.
Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Ann Oncol. 2025 Apr 8. doi: 10.1016/j.annonc.2025.03.023.
The cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) palbociclib, ribociclib and abemaciclib in combination with endocrine therapy (ET) are the standard-of-care, first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR-positive/HER2-negative aBC). However, no large head-to-head comparisons of the three CDK4/6is have been conducted so far.
We carried out a multicenter, observational, population-based study to compare the effectiveness of first-line palbociclib, ribociclib and abemaciclib in combination with ET in consecutive HR-positive/HER2-negative aBC patients who initiated the treatment between January 2016 and September 2023 in 18 Italian cancer centers. The primary study endpoint was real-world progression-free survival (rwPFS). Multivariable Cox regression models were used to adjust the association between individual CDK4/6i and rwPFS for clinically relevant variables.
Of 1982 patients enrolled in the PALMARES-2 study, 789, 736 and 457 patients received palbociclib, ribociclib and abemaciclib, respectively. Median rwPFS was 34.1 months. In the whole study cohort, abemaciclib and ribociclib were associated with better rwPFS when compared with palbociclib [adjusted hazard ratio (aHR) 0.76, 95% confidence interval (CI) 0.63-0.92, P = 0.004 and aHR 0.83, 95% CI 0.73-0.95, P = 0.007, respectively]. In patients with endocrine-sensitive disease, only abemaciclib was associated with better rwPFS when compared with palbociclib. On the contrary, abemaciclib and ribociclib were more effective than palbociclib in patients who were premenopausal or had endocrine-resistant or luminal B-like disease, while abemaciclib was more effective than ribociclib and palbociclib in patients with de novo metastatic disease, and more effective than palbociclib in patients with poorer Eastern Cooperative Oncology Group performance status. The three CDK4/6is were similarly effective in patients who were older or had bone-only disease.
Palbociclib, ribociclib and abemaciclib have different real-world effectiveness in HR-positive/HER2-negative aBC patients. Our findings can support clinicians in choosing the most appropriate CDK4/6i in specific clinical contexts.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）哌柏西利、瑞博西尼和阿贝西利联合内分泌治疗（ET）是激素受体阳性、人表皮生长因子受体2阴性晚期乳腺癌（HR阳性/HER2阴性aBC）患者的标准一线治疗方案。然而，目前尚未对这三种CDK4/6i进行大规模的直接比较。
我们开展了一项多中心、观察性、基于人群的研究，以比较2016年1月至2023年9月期间在18家意大利癌症中心开始接受治疗的连续HR阳性/HER2阴性aBC患者中，一线使用哌柏西利、瑞博西尼和阿贝西利联合ET的疗效。主要研究终点是真实世界无进展生存期（rwPFS）。采用多变量Cox回归模型，针对临床相关变量调整个体CDK4/6i与rwPFS之间的关联。
在PALMARES-2研究纳入的1982例患者中，分别有789例、736例和457例患者接受了哌柏西利、瑞博西尼和阿贝西利治疗。rwPFS的中位数为34.1个月。在整个研究队列中，与哌柏西利相比，阿贝西利和瑞博西尼与更好的rwPFS相关[调整后风险比（aHR）分别为0.76，95%置信区间（CI）0.63 - 0.92，P = 0.004；aHR为0.83，95% CI 0.73 - 0.95，P = 0.007]。在内分泌敏感型疾病患者中，与哌柏西利相比，只有阿贝西利与更好的rwPFS相关。相反，在绝经前或患有内分泌抵抗性或管腔B样疾病的患者中，阿贝西利和瑞博西尼比哌柏西利更有效；在初发转移性疾病患者中，阿贝西利比瑞博西尼和哌柏西利更有效；在东部肿瘤协作组体能状态较差的患者中，阿贝西利比哌柏西利更有效。在年龄较大或仅患有骨转移疾病的患者中，这三种CDK4/6i的疗效相似。
哌柏西利、瑞博西尼和阿贝西利在HR阳性/HER2阴性aBC患者中的真实世界疗效不同。我们的研究结果可为临床医生在特定临床情况下选择最合适的CDK4/6i提供参考。
