Allen Jeffrey W, Moon James, Redman Mary, Gadgeel Shirish M, Kelly Karen, Mack Philip C, Saba Hanna M, Mohamed Mohamed K, Jahanzeb Mohammad, Gandara David R
Jeffrey W. Allen, University of Tennessee Health Science Center, Memphis, TN; James Moon, Mary Redman, Southwest Oncology Group Statistical Center, Seattle, WA; Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State University, Detroit, MI; Karen Kelly, Phillip C. Mack, David R. Gandara, University of California Davis Cancer Center, Sacramento, CA; Hanna M. Saba, Central Illinois CCOP/Cancer Care Specialists of Central Illinois, Effingham, IL; Mohamed K. Mohamed, Moses Cone Health System, Greensboro, NC; and Mohammad Jahanzeb, University of Miami, Miami, FL.
J Clin Oncol. 2014 Aug 10;32(23):2463-70. doi: 10.1200/JCO.2013.51.4109. Epub 2014 Jul 7.
Development of new therapies for previously treated small-cell lung cancer (SCLC) is a major unmet need. Here, we describe a randomized, phase II trial of weekly topotecan with or without ziv-aflibercept (VEGF-trap) in this clinical setting.
Patients with previously treated SCLC (one line of platinum-based chemotherapy), performance status of 0 to 1, adequate organ function, treated brain metastases, and no recent vascular events or bleeding diatheses were eligible. Eligible patients were stratified as platinum-sensitive or platinum-refractory and randomly assigned to receive weekly topotecan 4 mg/m(2) intravenously (IV) with or without ziv-aflibercept 6 mg/kg IV every 21 days. Progression-free survival (PFS) at 3 months was the primary end point.
In 189 randomly assigned patients, treatment arms were well balanced with regard to clinical characteristics. The 3-month PFS was significantly improved with the addition of ziv-aflibercept in patients who had platinum-refractory disease (27% v 10%; P = .02) but not in patients with platinum-sensitive disease (24% v 15%; P = .22). Although response rate was low, disease control rate was higher with combination therapy than with topotecan alone in patients who had platinum-sensitive disease (37% v 18%; P = .05) and in those who had platinum-refractory disease (25% v 15%; P = .14). Overall survival (OS) was not significantly improved in either strata. Grades 3 to 5 toxicities were more common with the addition of ziv-aflibercept.
Ziv-aflibercept improved the 3-month PFS in patients who had platinum-refractory SCLC, but its addition increased toxicity. OS was similar with combined ziv-aflibercept and topotecan compared with topotecan in both strata.
开发针对既往接受过治疗的小细胞肺癌（SCLC）的新疗法是一项尚未满足的重大需求。在此，我们描述了在这种临床环境下每周使用拓扑替康联合或不联合西伐珠单抗（VEGF 陷阱）的随机 II 期试验。
既往接受过治疗的 SCLC 患者（一线铂类化疗），体能状态为 0 至 1，器官功能良好，有脑转移瘤且近期无血管事件或出血性疾病者符合条件。符合条件的患者被分层为铂敏感或铂耐药，并随机分配接受每周静脉注射 4mg/m²拓扑替康，联合或不联合每 21 天静脉注射 6mg/kg 西伐珠单抗。3 个月时的无进展生存期（PFS）是主要终点。
在 189 例随机分配的患者中，各治疗组在临床特征方面均衡良好。在铂耐药疾病患者中，添加西伐珠单抗使 3 个月 PFS 显著改善（27%对 10%；P = 0.02），但在铂敏感疾病患者中未改善（24%对 15%；P = 0.22）。虽然缓解率较低，但联合治疗的疾病控制率在铂敏感疾病患者（37%对 18%；P = 0.05）和铂耐药疾病患者（25%对 15%；P = 0.14）中均高于单纯拓扑替康治疗。在两个分层中，总生存期（OS）均未显著改善。添加西伐珠单抗后 3 至 5 级毒性更常见。
西伐珠单抗改善了铂耐药 SCLC 患者的 3 个月 PFS，但添加后增加了毒性。在两个分层中，西伐珠单抗与拓扑替康联合治疗的 OS 与单纯拓扑替康相似。
