白蛋白结合型纳米紫杉醇＋卡铂：一线治疗三阴性转移性乳腺癌患者

　　编者按：转移性三阴性乳腺癌预后较差、复发和死亡较快。目前，此类乳腺癌的治疗主要依靠紫杉类、铂类联合化疗。不过，由于紫杉醇的水溶性低、过敏性高，注射之前需要使用有机溶剂和抗过敏药。白蛋白结合型纳米紫杉醇不需要预处理即可注射，有效性和安全性得到显著提高。吉西他滨为嘧啶类抗肿瘤药物，可以阻断细胞有丝分裂周期由DNA合成前期（G1期）进入DNA合成期（S期），联合紫杉类或铂类对三阴性乳腺癌有效。

　　2018年6月6日，欧洲肿瘤内科学会和牛津大学出版社旗下《肿瘤学年鉴》在线发表美国莎拉·坎农研究所、田纳西肿瘤医院集团、匹兹堡大学医学院、艾荣坞肿瘤医院、沃思堡癌症与血液疾病中心、亨利·福特医院集团、佛罗里达肿瘤医院集团、德克萨斯肿瘤医院集团、贝勒医学院查尔斯·萨蒙斯癌症中心、赛尔基因（新基）公司、英国谢菲尔德大学威斯顿公园医院、意大利帕多瓦大学威尼托肿瘤研究所、格罗塞托慈善综合医院、西班牙马德里大学拉蒙卡哈尔医院、瓦尔德希布伦肿瘤研究所、塞维利亚大学马卡丽娜圣女医院、德国海德堡大学医院、慕尼黑大学的tnAcity研究报告，比较了白蛋白结合型纳米紫杉醇＋卡铂或吉西他滨、吉西他滨＋卡铂一线治疗三阴性转移性乳腺癌患者的有效性和安全性。

tnAcity: Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

　　该多中心非盲随机对照II期研究于2013年9月26日～从11个国家入组经病理确认未三阴性乳腺癌转移后尚未接受化疗患者191例，按1∶1∶1随机分配接受白蛋白结合型纳米紫杉醇125mg/m²＋卡铂AUC2（64例）、白蛋白结合型纳米紫杉醇125mg/m²＋吉西他滨1000mg/m²（61例）、吉西他滨1000mg/m²＋卡铂AUC2（66例），均为每3周第1、8天用药。主要研究终点：由研究者评定的无进展生存；次要研究终点包括总缓解率、总生存、完成6周期两药联合治疗的患者百分比、安全性。结果发现：

　　中位无进展生存时间：

• 紫杉＋卡铂：8.3个月

• 紫杉＋吉西：5.5个月（风险比：0.59，95%置信区间：0.38～0.92，P=0.02）

• 吉西＋卡铂：6.0个月（风险比：0.58，95%置信区间：0.37～0.90，P=0.02）

　　中位总生存时间：

• 紫杉＋卡铂：16.8个月

• 紫杉＋吉西：12.1个月（风险比：0.73，95%置信区间：0.47～1.13，P=0.16）

• 吉西＋卡铂：12.6个月（风险比：0.80，95%置信区间：0.52～1.22，P=0.29）

　　总缓解率：

• 紫杉＋卡铂：73%

• 紫杉＋吉西：39%

• 吉西＋卡铂：44%

　　完成6周期两药联合治疗的患者百分比：

• 紫杉＋卡铂：64%

• 紫杉＋吉西：56%

• 吉西＋卡铂：50%

　　3级以上不良事件以血液学为主。

　　因此，白蛋白结合型纳米紫杉醇＋卡铂一线治疗转移性三阴性乳腺癌有效，与白蛋白结合型纳米紫杉醇＋吉西他滨、吉西他滨＋卡铂相比，无进展生存时间显著较长，风险与获益比改善。

Ann Oncol. 2018 Jun 6. [Epub ahead of print]

nab-Paclitaxel Plus Carboplatin or Gemcitabine vs Gemcitabine Plus Carboplatin as First-Line Treatment for Patients With Triple-Negative Metastatic Breast Cancer: Results From the tnAcity Trial.

D A Yardley; R Coleman; P Conte; J Cortes; A Brufsky, M Shtivelband, R Young C Bengala, H Ali, J Eakel, A Schneeweiss, L de la Cruz-Merino, S Wilks, J O'Shaughnessy, S Glück, H Li, J Miller, D Barton, N Harbeck, tnAcity investigators.

Sarah Cannon Research Institute and Tennessee Oncology PLLC, Nashville, TN, USA; Weston Park Hospital, University of Sheffield, Sheffield, UK; University of Padova, Istituto Oncologico Veneto, Padova, Italy; Ramon y Cajal University Hospital, Madrid and Vall d'Hebron Institute of Oncology, Barcelona, Spain; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Ironwood Physicians, Chandler, AZ, USA; The Center for Cancer and Blood Disorders, Fort Worth, TX, USA; Misericordia General Hospital, Grosseto, Italy; Henry Ford Health System, Detroit, MI, USA; Florida Cancer Specialists, Sarasota, FL, USA; Heidelberg University Hospital, Heidelberg, Germany; Hospital Universitario Virgen Macarena, Seville, Spain; Texas Oncology, San Antonio, TX, USA; Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, USA; Celgene Corporation, Summit, NJ, USA; University of Munich, Munich, Germany.

BACKGROUND: Metastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and/safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC.

PATIENTS AND METHODS: Patients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1:1:1) nab-P 125mg/m2 plus C AUC 2, nab-P 125mg/m2 plus G 1000mg/m2, or G 1000mg/m2 plus C AUC 2, all on days 1, 8 q3w. Phase II primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety.

RESULTS: In total, 191 patients were enrolled (nab-P/C, n=64; nab-P/G, n=61; G/C, n=66). PFS was significantly longer with nab-P/C vs nab-P/G (median, 8.3 vs 5.5 months; HR, 0.59 [95% CI, 0.38-0.92]; P = .02) or G/C (median, 8.3 vs 6.0 months; HR, 0.58 [95% CI, 0.37-0.90]; P = .02). OS was numerically longer with nab-P/C vs nab-P/G (median, 16.8 vs 12.1 months; HR, 0.73 [95% CI, 0.47-1.13]; P = .16) or G/C (median, 16.8 vs 12.6 months; HR, 0.80 [95% CI, 0.52-1.22]; P = .29). ORR was 73%, 39%, and 44% respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic.

CONCLUSIONS: First-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile vs nab-P/G or G/C.

KEYWORDS: Chemotherapy, triple negative breast cancer, nab-paclitaxel, gemcitabine

DOI: 10.1093/annonc/mdy201

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