Ogata Nanae, Barnett Brian G, Sharp Nicholas J H, Fujii Takeo, Iwase Toshiaki, Dunn Sandra E, Ueno Naoto T
Translational and Clinical Research Program, University of Hawai'i Cancer Center, Honolulu, HI 96813, USA.
Cancer Biology Program, University of Hawai'i Cancer Center, Honolulu, HI 96813, USA.
Cancers (Basel). 2025 Mar 4;17(5):884. doi: 10.3390/cancers17050884.
Guidelines for the first-line treatment of Hormone Receptor-positive, HER2-negative advanced or recurrent breast cancer have shifted to combination therapies of a CDK4/6 inhibitor and endocrine therapy. However, determining an optimal subsequent therapy following CDK4/6 inhibitor progression remains challenging, especially for tumors lacking actionable mutations. Real-world data suggest that fulvestrant monotherapy is frequently selected in this post-CDK4/6 inhibitor setting. This review examines its therapeutic potential in this evolving landscape. A systematic literature search using PubMed and ClinicalTrials.gov identified 153 clinical trials published between 2017 and November 2024, from which ten studies met our strict inclusion criteria, focusing solely on fulvestrant monotherapy. These trials encompassed 1038 patients who had prior exposure to CDK4/6 inhibitors. The selected studies were categorized into three groups: monotherapy trials (EMERALD, SERENA-2, AMEERA-3, and ELAINE-1), combination therapy trials (CAPItello-291 and VERONICA), and CDK4/6 inhibitor rechallenge trials (post-MONARCH, PACE, PALMIRA, and MAINTAIN). The median progression-free survival for fulvestrant monotherapy was 3.18 months (range 1.9-5.3 months). Factors affecting the efficacy of fulvestrant monotherapy in second-line therapy include prior treatments, treatment duration, and genetic mutations. Given that the efficacy of fulvestrant was short-lived in the second or subsequent lines, participating in clinical trials is a vital option until a novel alternative treatment choice becomes available.
激素受体阳性、人表皮生长因子受体2阴性晚期或复发性乳腺癌的一线治疗指南已转向CDK4/6抑制剂与内分泌治疗的联合疗法。然而，在CDK4/6抑制剂进展后确定最佳的后续治疗仍然具有挑战性，尤其是对于缺乏可操作突变的肿瘤。真实世界数据表明，在CDK4/6抑制剂治疗后的这种情况下，氟维司群单药治疗经常被选用。本综述探讨了其在这一不断演变的格局中的治疗潜力。通过使用PubMed和ClinicalTrials.gov进行系统的文献检索，确定了2017年至2024年11月期间发表的153项临床试验，其中有10项研究符合我们严格的纳入标准，仅聚焦于氟维司群单药治疗。这些试验纳入了1038例先前接受过CDK4/6抑制剂治疗的患者。所选研究分为三组：单药治疗试验（EMERALD、SERENA-2、AMEERA-3和ELAINE-1）、联合治疗试验（CAPItello-291和VERONICA）以及CDK4/6抑制剂再挑战试验（post-MONARCH、PACE、PALMIRA和MAINTAIN）。氟维司群单药治疗的中位无进展生存期为3.18个月（范围1.9 - 5.3个月）。影响氟维司群单药二线治疗疗效的因素包括先前的治疗、治疗持续时间和基因突变。鉴于氟维司群在二线或后续治疗中的疗效持续时间较短，在有新的替代治疗选择出现之前，参与临床试验是一个至关重要的选择。
