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
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands.
Nature. 2024 Dec;636(8042):474-480. doi: 10.1038/s41586-024-08035-2. Epub 2024 Nov 27.
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 treatment. 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 setting. 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.
细胞周期蛋白依赖性激酶4和6抑制剂（CDK4/6i）与内分泌治疗联合应用可改善激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性晚期乳腺癌患者的预后，可早期作为一线治疗使用，也可推迟至二线治疗。目前缺乏比较CDK4/6i在一线和二线治疗中应用的随机数据。3期SONIA试验（NCT03425838）将1050例既往未接受过晚期乳腺癌治疗的患者随机分为一线或二线接受CDK4/6i治疗。所有患者均接受相同的内分泌治疗，一线治疗采用芳香化酶抑制剂，二线治疗采用氟维司群。主要终点定义为从随机分组到二线治疗后疾病进展的时间（无进展生存期2（PFS2））。我们观察到，与二线治疗相比，一线使用CDK4/6i没有统计学上的显著益处（中位数分别为31.0个月和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的CDK4/6i治疗持续时间更长（CDK4/6i治疗持续时间中位数分别为24.6个月和8.1个月），且≥3级不良事件更多（分别为2763例和1591例）。这些数据对所有患者一线使用CDK4/6i的必要性提出了质疑。
