美国食品药品监督管理局（FDA）已经先后批准了三种细胞周期蛋白依赖型激酶4/6（CDK4/6）抑制剂：哌柏西利、瑞波西利、阿贝西利。不过，晚期乳腺癌老年女性对于此类药物联合芳香酶抑制剂的有效性和安全性尚不明确。
2019年9月27日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国食品药品监督管理局（FDA）汇总分析报告，比较了芳香酶抑制剂±CDK4/6抑制剂治疗激素受体阳性、HER2阴性晚期乳腺癌老年女性的有效性和安全性。
该研究汇总了三种不同CDK4/6抑制剂联合芳香酶抑制剂一线治疗激素受体阳性、HER2阴性晚期乳腺癌绝经后女性的3项随机对照研究共计1827例患者数据，通过生存曲线推算和多因素比例风险回归模型，评估年龄对无进展生存的影响。
结果，芳香酶抑制剂±CDK4/6抑制剂相比，198例年龄≥75岁患者的复发或死亡风险低51%（风险比：0.49，95%置信区间：0.31～0.76），推算中位无进展生存为31.1比13.7个月（95%置信区间：20.2～未达，10.9～24.9）。
3～4级不良事件发生率：年龄≥75岁患者为88.8%，年龄<75岁患者为73.4%。无论芳香酶抑制剂±CDK4/6抑制剂，年龄≥75岁患者自评生活质量EQ-5D评分均降低。
因此，该研究结果表明，三种芳香酶抑制剂＋CDK4/6抑制剂与单用芳香酶抑制剂相比，一线治疗激素受体阳性、HER2阴性晚期乳腺癌老年女性与年轻患者的有效性相似，年龄≥75岁患者的毒性反应发生率较高、剂量调整比例较高、生活质量指标较基线水平降低。
J Clin Oncol. 2019 Sep 27. [Epub ahead of print]
Outcomes of Older Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer Treated With a CDK4/6 Inhibitor and an Aromatase Inhibitor: An FDA Pooled Analysis.
Howie LJ, Singh H, Bloomquist E, Wedam S, Amiri-Kordestani L, Tang S, Sridhara R, Sanchez J, Prowell TM, Kluetz PG, King-Kallimanis BL, Gao JJ, Ibrahim A, Goldberg KB, Theoret M, Pazdur R, Beaver JA.
US Food and Drug Administration, White Oak, MD.
PURPOSE: Many older women will be treated with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and an aromatase inhibitor (AI), given US Food and Drug Administration approval of three agents in this class. The current pooled analysis examines the efficacy and safety of this combination in older women.
PATIENTS AND METHODS: We pooled data from three randomized controlled studies (N = 1,827) of different CDK4/6 inhibitors in combination with an AI for initial treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. The effect of age on progression-free survival was evaluated using Kaplan-Meier estimates and a Cox proportional hazards regression model.
RESULTS: For patients age 75 years or older (n = 198) who were treated with a CDK4/6 inhibitor and an AI, hazard ratio was 0.49 (95% CI, 0.31 to 0.76) with an estimated median progression-free survival of 31.1 months (95% CI, 20.2 months to not reached) versus 13.7 months (95% CI, 10.9 months to 24.9 months) for those treated with an AI. Incidence of grade 3 to 4 adverse events was 88.8% in patients age 75 years and older and 73.4% in patients younger than age 75 years. Patients age 75 years or older reported a decline in quality-of-life measures using the EQ-5D regardless of treatment with AI alone or with the addition of a CDK4/6 inhibitor.
CONCLUSION: There was similar efficacy with a CDK4/6 inhibitor in combination with an AI compared with AI alone for first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer in older women compared with younger patients. Patients older than age 75 years experienced higher rates of toxicity, dose modifications, and a decrease from baseline in quality-of-life measures.
PMID: 31560580
DOI: 10.1200/JCO.18.02217
联系客服
