卡培他滨对早期三阴乳腺癌化疗的作用
早期三阴性乳腺癌可以通过标准的手术、放疗等局部区域疗法＋术后辅助化疗治愈。不过，与非三阴性乳腺癌相比，仍有部分患者复发风险较高。2017年美国麻省医学会《新英格兰医学杂志》发表的日本JBCRG04研究暨韩国CREATE-X研究最终结果表明，对于HER2阴性乳腺癌术前标准新辅助化疗失败患者，联合卡培他滨可以安全有效地改善术后辅助化疗的无病生存和总生存。不过，卡培他滨辅助治疗对于早期三阴性乳腺癌标准新辅助或辅助化疗后患者的有效性和安全性存在争议。
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2019年12月5日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表西班牙乳腺癌研究协作组、伊比利亚美洲乳腺肿瘤研究联盟、拉丁美洲肿瘤学研究协作组的研究报告，对早期三阴性乳腺癌患者完成标准新辅助或辅助化疗后，卡培他滨辅助治疗的有效性和安全性进行了探讨。
该国际多中心非盲随机对照三期临床研究于2006年10月～2011年9月从西班牙、巴西、智利、哥伦比亚、厄瓜多尔、墨西哥、秘鲁、委内瑞拉的80家医院，入组可手术、淋巴结阳性（或淋巴结阴性且肿瘤≥1厘米）三阴性乳腺癌、已经蒽环类和（或）紫杉类新辅助或辅助化疗患者876例。通过免疫组织化学法对三阴性乳腺癌状态进行集中确认后，将患者随机分入卡培他滨组或观察组。分层分析因素包括医院、过去紫杉类治疗、腋窝淋巴结转移、通过免疫组织化学法根据细胞角蛋白5/6和（或）表皮生长因子受体阳性集中确定的基底样或非基底表现型。主要研究终点为无病生存。
结果，卡培他滨组患者448例、观察组患者428例。中位年龄49岁，淋巴结阴性占55.9%，基底样表现型占73.9%，曾经蒽环类＋紫杉类化疗占67.5%。
中位随访7.3年期间，卡培他滨组与观察组的全部患者相比，复发死亡比例相似（23.4%比28%，风险比：0.82，95%置信区间：0.63～1.06，P=0.136）。
根据预设亚组分析，非基底与基底样表现型的全部患者相比：
复发死亡风险比：0.53比0.94（相互影响分析，P=0.0694）
总的死亡风险比：0.42比1.23（相互影响分析，P=0.0052）
卡培他滨耐受性符合预期，其中75.2%的患者按计划完成8个周期。
因此，该研究结果表明，对于早期三阴性乳腺癌患者，标准化疗±卡培他滨辅助治疗相比，无病生存结局相似。根据预设亚组分析，非基底与基底样表现型的患者相比，可能对卡培他滨辅助治疗获益，不过需要进一步验证。
对此，美国费城福克斯蔡斯癌症中心发表同期述评：卡培他滨对早期乳腺癌的作用。
J Clin Oncol. 2019 Dec 5. [Epub ahead of print]
Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01).
Lluch A, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Guerrero-Zotano A, García-Sáenz JA, Torres R, de la Haba J, García-Martínez E, Gómez HL, Llombart A, Bofill JS, Baena-Canada JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M, Fernández I, Rodríguez-Lescure A, Cárdenas J, Vinholes J, Martínez de Duenas E, Godes MJ, Seguí MA, Antón A, López-Alvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Martín M; GEICAM Spanish Breast Cancer Group; CIBOMA (Iberoamerican Coalition for Research in Breast Oncology); LACOG (Latin American Cooperative Oncology Group).
University of Valencia, Valencia, Spain; Instituto Valenciano de Oncología, Valencia, Spain; Hospital General Universitario de Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red de Oncología ISCIII, Madrid, Spain; GEICAM, Spanish Breast Cancer Group, Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain; Universidad Complutense, Madrid, Spain; Hospital Universitario Virgen del Rocío, Sevilla, Spain; Hospital Universitario Na Sa de Valme, Sevilla, Spain; Hospital Universitario Reina Sofía, Córdoba, Spain; Hospital General Universitario Morales Meseguer, Murcia, Spain; Hospital Arnau de Vilanova, Lleida, Spain; Hospital Universitario Puerta del Mar and Instituto de Investigación e Innovación Biomédica de Cádiz, Cádiz, Spain; Hospital de la Santa Creu i Sant Pau, Universitat Autonoma, Institut Recerca Biomedica Sant Pau, Barcelona, Spain; Corporació Sanitaria Parc Taulí de Sabadell, Barcelona, Spain; Complexo Hospitalario Universitario A Coruna, A Coruna, Spain; Centro Oncológico de Galicia, A Coruna, Spain; Complexo Hospitalario Universitario de Vigo, Vigo, Spain; Hospital General Universitario de Elche, Alicante, Spain; Consorcio Hospitalario Provincial de Castellón, Castellón, Spain; Hospital Universitario Miguel Servet, Zaragoza, Spain; Hospital Nuestra Senora de la Candelaria, Santa Cruz de Tenerife, Spain; Hospital Regional Universitario Carlos Haya, Málaga, Spain; Centro de Pesquisa Clínica Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil; LACOG, Latin American Cooperative Oncology Group, Porto Alegre, Brazil; Unidade de Novos Tratamentos CliniOnco, Porto Alegre, Brazil; Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Oncologistas Associados-Oncologia D'Or, Rio de Janeiro, Brazil; Hospital Amaral Carvalho, Sao Paolo, Brazil; Clínica Amo Itaigara, Salvador, Brazil; Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México; Hospital de San José, Ciudad Obregón, Sonora, México; Centro Médico Colima, Colima, México; Hospital Beneficiencia Espanola, San Luis de Potosí, México; Instituto Nacional del Cáncer, Santiago, Chile; Hospital Base de Valdivia, Valdivia, Chile; Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú; GECOPERU, Peruvian Oncological Clinical Studies Group, Lima, Peru; Social S Hospital Teodoro Maldonado Carbo, Guayaquil, Ecuador.
PURPOSE: Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC.
PATIENTS AND METHODS: Eligible patients were those with operable, node-positive (or node negative with tumor 1 cm or greater) TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms.
RESULTS: Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = 0.136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = 0.0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = 0.0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles.
CONCLUSION: This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation.
PMID: 31804894
DOI: 10.1200/JCO.19.00904
J Clin Oncol. 2019 Dec 5. [Epub ahead of print]
Role of Capecitabine in Early Breast Cancer.
Varshavsky-Yanovsky AN, Goldstein LJ.
Fox Chase Cancer Center, Philadelphia, PA.
PMID: 31804861
DOI: 10.1200/JCO.19.02946