荷兰癌症研究所Gabe S. Sonke团队近期取得重要工作进展，他们对晚期乳腺癌患者早期使用CDK4/6抑制剂与推迟使用CDK4/6抑制剂进行了比较，相关研究成果2024年11月27日在线发表于《自然》杂志上。

据介绍，细胞周期依赖性激酶4和6抑制剂（CDK4/6i）与内分泌治疗相结合，可改善激素受体（HR）阳性、HER2阴性晚期癌症患者的预后，可早期用作一线治疗或推迟到二线治疗。目前缺乏比较CDK4/6i在一线和二线设置中使用的随机数据。

SONIA 3期试验（NCT03425838）将1050名既往未接受过晚期癌症治疗的患者，随机分为一线或二线接受CDK4/6i治疗。所有患者都接受了相同的内分泌治疗，包括一线治疗的芳香化酶抑制剂和二线治疗的氟维司群。主要终点定义为从随机化到二线治疗后疾病进展的时间（无进展生存期2（PFS2））。

研究人员观察到，与二线治疗相比，CDK4/6i作为一线治疗没有统计学上的显著益处（中位数分别为31.0和26.8个月；风险比 = 0.87；95%置信区间 = 0.74-1.03；P=0.10）。两组的健康相关生活质量相似。

与二线使用相比，一线使用CDK4/6i与更长的CDK4/6i治疗持续时间（CDK4/6l治疗持续时间中位数分别为24.6个月和8.1个月）和更多≥3级不良事件（分别为2763个和1591个）有关。这些数据挑战了所有患者一线使用CDK4/6i的必要性。

附：英文原文

Title: Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer

Author: Sonke, Gabe S., van Ommen-Nijhof, Annemiek, Wortelboer, Noor, van der Noort, Vincent, Swinkels, Astrid C. P., Blommestein, Hedwig M., Guerrero Paez, Cristina, Mol, Linda, Beeker, Aart, Beelen, Karin, Hamming, Lisanne C., Heijns, Joan B., Honkoop, Aafke H., de Jong, Paul C., van Rossum-Schornagel, Quirine C., van Schaik-van de Mheen, Christa, Tol, Jolien, Tromp-van Driel, Cathrien S., Vrijaldenhoven, Suzan, van Leeuwen-Stok, A. Elise, Konings, Inge R., Jager, Agnes

Issue&Volume: 2024-11-27

Abstract: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy improve the outcomes of patients with hormone-receptor (HR)-positive, HER2-negative advanced breast cancer and can be used early as first-line treatment or deferred to second-line treatment1,2,3,4,5,6,7. Randomized data comparing the use of CDK4/6i in the first- and second-line setting are lacking. The phase 3 SONIA trial (NCT03425838) randomized 1,050 patients who had not received previous therapy for advanced breast cancer to receive CDK4/6i in the first- or second-line setting8. All of the patients received the same endocrine therapy, consisting of an aromatase inhibitor for first-line treatment and fulvestrant for second-line treatment. The primary end point was defined as the time from randomization to disease progression after second-line treatment (progression-free survival 2 (PFS2)). We observed no statistically significant benefit for the use of CDK4/6i as a first-line compared with second-line treatment (median, 31.0 versus 26.8 months, respectively; hazard ratio=0.87; 95% confidence interval=0.74–1.03; P=0.10). The health-related quality of life was similar in both groups. First-line CDK4/6i use was associated with a longer CDK4/6i treatment duration compared with second-line use (median CDK4/6i treatment duration of 24.6 versus 8.1 months, respectively) and more grade ≥3 adverse events (2,763 versus 1,591, respectively). These data challenge the need for first-line use of a CDK4/6i in all patients.

DOI: 10.1038/s41586-024-08035-2

Source: https://www.nature.com/articles/s41586-024-08035-2