中国乳腺癌研究入选美国临床肿瘤年会口头报告

　　2016年6月3～7日，美国临床肿瘤学会（ASCO）第52届年会将在美国芝加哥召开。作为肿瘤领域一年一度最重磅的会议，越来越多的中国肿瘤专家学者在ASCO年会上大放异彩，今年有一项乳腺癌研究入选ASCO的口头报告，让我们一起来看看吧！

　　晚期乳腺癌化疗：基因工程埃博霉素类似物微管稳定剂（utidelone）联合卡培他滨（CAP）优于CAP单药

　　时间：2016年6月4日14:27～14:39（美国当地时间）

　　地点：乳腺癌——三阴性/细胞毒化疗/局部疗法口头报告分会场

　　报告人：徐兵河教授（代表中国医学科学院肿瘤医院、辽宁省肿瘤医院、哈尔滨医科大学附属肿瘤医院、中山大学肿瘤防治中心/华南肿瘤学国家重点实验室/肿瘤医学协同创新中心、浙江省肿瘤医院、河南省肿瘤医院、军事医学科学院附属医院、中国医科大学附属第一医院、复旦大学附属肿瘤医院）

　　该Ⅲ期研究入组北京、沈阳、哈尔滨、广州、杭州、郑州、上海九家医院经紫杉类和蒽环类化疗药物治疗失败（80%≥2个化疗方案）的晚期乳腺癌患者405例，2∶1随机分入CAP（1000mg/m²，po，bid，d1～14）＋utidelone（30mg/m²，iv，d1～5）联合组或CAP（1250mg/m²，po，bid，d1～14）单药组，每周期21天，直至疾病进展或毒性反应无法接受，研究主要终点为无进展生存（PFS），次要终点为客观缓解率（ORR）、安全性、总生存（至2017年）。

　　结果发现，显示联合组较单药组PFS（危害比0.58；95%置信区间：0.44～0.75；P＜0.0001）和ORR（39.4%比28.9%，联合组有2例完全缓解）显著改善。联合组的肝肾毒性低，骨髓移植无显著提高。联合组与单药组相比，3/4级不良事件包括周围神经病变（14.2%比0%）、手足综合征（10%比6.7%）、恶心（1.5%比1.5%）、高胆红素血症（0%比1.5%）、腹泻（5%比0%）、贫血（3.1%比3%）、白细胞减少（4.2%比5.2%）和中性粒细胞（6.5%比5.2%）。

　　该研究为今年唯一一项入选口头报告的中国乳腺癌研究。

J Clin Oncol. 2016;34(suppl):A1004.

Randomized phase III trial of utidelone, a genetically engineered epothilone analog, in combination with capecitabine versus capecitabine alone for metastatic breast cancer patients with previous taxane and anthracycline treatment.

Binghe Xu, Tao Sun, Qingyuan Zhang, Zhongyu Yuan, Pin Zhang, Wang Xiao Jia, Shude Cui, Zefei Jiang, Yuee Teng, Xi-Chun Hu.

Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China; Liaoning Cancer Hospital and Institute, Liaoning, China; Harbin Medical University Cancer Hospital, Harbin, China; Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Zhejiang Cancer Hospital, Zhejiang, China; Cancer Center of Henan Province, Zhengzhou, China; The 307th Hospital of Chinese PLA, Beijing, China; First Hospital of China Medical University, Shenyang, China; Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Utidelone, a genetically engineered epothilone analog, is a microtubule stabilizing agent that showed promising activities in phase I and phase II trials. In this report, a multi-center, randomized phase III trial of utidelone plus capecitabine (CAP) vs CAP alone wascarried out to assess the efficacy and safety.

Methods: Patients with metastatic breast cancer (MBC) previously treated with anthracycline and taxanes were randomized to utidelone (30mg/m2/d intravenously on d1-d5) plus CAP (1,000 mg/m2 orally bid on d1-d14) or CAP alone (1,250 mg/m2 orally bid on d1-d14) given every 21 days, until disease progression or unacceptable toxicity occurred. The two arms were enrolled with 2:1 ratio. The primary endpoint is progression-free survival (PFS); secondary endpoints include objective response rate (ORR), safety, and overall survival (available by 2017). PFS was estimated using the Kaplan-Meier product-limit method.

Results: Of 405 patients randomized, about 80% had more than two prior chemotherapy regimens. Median of 6 and 5 cycles of utidelone plus CAP and CAP alone, respectively, were administered. The combination of utidelone with CAP was superior to CAP alone for both PFS (hazard ratio= 0.58; 95% CI, 0.44 to 0.75; log-rank P <0.0001) and ORR (39.4% with 2 complete responses vs 28.9% in the monotherapy arm). utidelone plus CAP showed low level of liver and renal toxicities, and did not have significant increase in myelosuppression. Grade3/4 adverse events included peripheral neuropathy (14.2% in combination arm vs 0% in CAP alone), hand-foot syndrome (10% vs 6.7%), nausea (1.5% vs 1.5%), hyperbilirubinaemia (0% vs 1.5%), diarrhea (5% vs 0%), anaemia (3.1% vs 3%), leukopenia(4.2% vs 5.2%) and neutropenia (6.5% vs 5.2%).

Conclusions: Utidelone plus CAP significantly improved PFS and ORR and had a manageable safety profile in this heavily pretreated population. It had very limited myelosuppression in addition to low liver and renal toxicities, in contrast to ixabepilone and other epothilone analogs. It offers a new potential therapeutic option for patients with MBC.

Clinical trial information: NCT02253459