Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial
Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial
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DOI：
10.1200/jco.19.00647
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发表时间：
2019-09-10
影响因子：
45.3
通讯作者：
Carey, Lisa
中科院分区：
文献类型：
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作者：
Muss, Hyman B.;Polley, Mei-Yin C.;Carey, Lisa
老年乳腺癌患者在临床试验中的代表性仍然不足。癌症和白血病组B 49907试验主要针对65岁及以上的女性。我们之前报道了中位随访2.4年后的主要分析。与卡培他滨相比，标准辅助化疗在无复发生存期（RFS）和总生存期方面有显著改善。我们现在更新了中位随访11.4年的结果。患者和方法年龄65岁或以上的早期乳腺癌患者被随机分配到标准辅助化疗（医生选择环磷酰胺，甲氨蝶呤，氟尿嘧啶或环磷酰胺和阿霉素）或卡培他滨。采用自适应贝叶斯设计确定样本量并检验卡培他滨的非劣效性。主要终点为RFS。结果在第一次样本量评估时，该设计停止了633例患者的招募。对于接受标准化疗的患者，RFS仍然显著更长。10年时，标准化疗组与卡培他滨组的RFS率分别为56%和50（风险比[HR]，0.80; P = 0.03）;乳腺癌特异性生存率分别为88%和82%，（HR，0.62; P = .03）;总生存率分别为62%和56%（HR，0.84; P = .16）。随着随访时间的延长，标准化疗在激素受体阴性患者中仍上级卡培他滨（HR，0.66; P = .02），但在激素受体阳性患者中则不然（HR，0.89; P = .43）。总体而言，43.9%的患者死亡（13.1%死于乳腺癌，16.4%死于乳腺癌以外的原因，14.1%死于不明原因）。其次是非乳腺癌，占14.1%。结论：随着随访时间的延长，标准辅助化疗的RFS仍然上级卡培他滨，尤其是在激素受体阴性疾病的患者中。老年人群中的竞争性风险稀释了总体生存获益。
PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.