对于晚期乳腺癌，口服化疗药物卡培他滨已被证实优于标准化疗。不过，卡培他滨对于早期乳腺癌的疗效存在争议。由于既往乳腺癌临床研究的老年比例不足，故美国肿瘤学临床研究联盟（ALLIANCE）癌症与白血病协作组（CALGB）第49907号研究重点关注了年龄≥65岁的早期乳腺癌老年女性，2009年报告的中位随访2.4年初步分析结果表明，术后标准辅助化疗与卡培他滨相比，无复发生存和总生存显著较好。
2019年7月24日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表北卡罗来纳大学莱恩伯格综合癌症中心、梅奥医学中心、德克萨斯大学MD安德森癌症中心、西北大学卢瑞综合癌症中心、纽约纪念医院斯隆凯特林癌症中心、伊利诺伊共济会医疗中心、哈佛大学达纳法伯癌症研究院、杜克大学癌症研究院、霍普金斯大学西德尼凯米尔癌症中心、华盛顿大学西雅图癌症联盟、寇恩医疗癌症中心、圣迭戈加利福尼亚大学摩尔斯癌症中心、哈罗德阿尔方德癌症治疗中心、希望之城综合癌症中心、加拿大圣博尼费斯综合医院的CALGB-49907研究中位随访11.4年最终分析报告。
CALGB-49907: A Randomized Trial of Adjuvant Chemotherapy With Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil - (CMF) or Doxorubicin and Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years and Older With Node Positive or Node-Negative Breast Cancer (NCT00024102)
该多中心非盲随机对照研究于2001年9月15日～2006年12月29日入组年龄≥65岁早期乳腺癌患者633例，按1∶1随机分组接受术后标准辅助化疗（由医师选择环磷酰胺＋甲氨蝶呤＋氟尿嘧啶或环磷酰胺＋多柔比星）或卡培他滨。通过贝叶斯自适应设计，确定样本大小并检验卡培他滨的非劣效性。主要终点为无复发生存。
结果，中位随访11.4年，标准化疗与卡培他滨相比：
全部患者无复发生存率较高：56%比50%（风险比：0.80，95%置信区间：0.62～0.98，P=0.03）
全部患者乳腺癌生存率较高：88%比82%（风险比：0.62，95%置信区间：0.39～0.97，P=0.03）
全部患者总生存率相似：62%比56%（风险比：0.84，95%置信区间：0.66～1.07，P=0.16）
激素受体阴性患者无复发生存率较高（风险比：0.66，95%置信区间：0.46～0.95，P=0.02）
激素受体阳性患者无复发生存率相似（风险比：0.89，95%置信区间：0.68～1.18，P=0.43）
患者总死亡率43.9%的，其中13.1%死于乳腺癌、16.4%死于乳腺癌以外原因、14.1%死于不明原因。非乳腺第二癌发生于14.1%的患者。
因此，该研究结果表明，经过长期随访，术后标准辅助化疗与卡培他滨相比，老年早期乳腺癌女性的无复发生存仍然较好，尤其对于激素受体阴性乳腺癌患者。不过，该老年人群的乳腺癌以外死亡原因竞争风险（例如心脑血管风险）削弱了术后标准辅助化疗的总生存获益。
J Clin Oncol. 2019 Jul 24. [Epub ahead of print]
Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.
Muss HB, Polley MC, Berry DA, Liu H, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Kartcheske PA, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Sutton LM, Magrinat G, Parker BA, Hart RD, Grenier D, Hurria A,, Jatoi A, Norton L, Hudis CA, Winer EP, Carey L.
University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston, TX; Robert H Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL; Memorial Sloan Kettering Cancer Center, New York, NY; Advocate Illinois Masonic Medical Center, Chicago, IL; Dana-Farber/Partners CancerCare, Boston, MA; Duke Cancer Institute, Duke University, Durham, NC; Mayo Clinic, Jacksonville, FL; Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD; University of Washington Seattle Cancer Alliance, Seattle, WA; Cone Health Cancer Center, Greensboro, NC; Moores Cancer Center, University of California San Diego, La Jolla, CA; Harold Alfond Center for Cancer Care, Augusta, ME; St Boniface General Hospital, Winnipeg, Manitoba, Canada; City of Hope Comprehensive Cancer Center, Duarte, CA.
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.
PMID: 31339827
DOI: 10.1200/JCO.19.00647
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