Li Qin, Yuan Zhenyan, Yan Han, Wen Zhaoyang, Zhang Ruixue, Cao Bangwei
Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China.
Experimental Center for Basic Medical Teaching, Capital Medical University, Beijing, People׳s Republic of China.
Clin Ther. 2014 Jul 1;36(7):1054-63. doi: 10.1016/j.clinthera.2014.05.066. Epub 2014 Jun 27.
Targeted therapy has brought great clinical benefits for patients with multiple solid tumors, but its effects in patients with locally advanced/metastatic pancreatic cancer (LA/MPC) are disputed. This systematic evaluation compared the efficacy and safety profiles of gemcitabine combined with targeted agents (GEM + TA) versus gemcitabine administered as monotherapy or combined with placebo (GEM ± PLC) in LA/MPC patients.
PubMed and EMBASE were searched for relevant randomized controlled trials published on or before April 30, 2013. The primary end points were overall survival (OS) and progression-free survival (PFS); the secondary end points were 1-year survival rate, objective response rate (ORR), and toxicity rates (TRs), defined as the prevalence of grade 3/4 adverse events. The systematic evaluation was performed by using Review Manager version 5.1.7.
A total of 10 randomized controlled trials involving 3899 patients (2195 males; mean age, 63.6 years) were included in the systematic evaluation. The results reported that there was no significant difference in OS (hazard ratio [HR] = 0.97 [P = 0.85]), PFS (HR = 0.95 [P = 0.14]), or ORR (odds ratio [OR] = 0.95 [P = 0.69]) between GEM + TA and GEM ± PLC. However, a marginal difference in 1-year survival rate (OR = 0.80 [P = 0.05]) between the 2 groups was observed. The grade 3/4 TRs of anemia, diarrhea, nausea, neutropenia, thrombocytopenia, and vomiting were not significantly different between the 2 groups. However, the prevalence of grade 3/4 rash was significantly greater in the GEM + TA group (OR = 8.31 [P < 0.01]).
Based on the results from this analysis, the addition of targeted agents to a regimen of gemcitabine treatment does not bring survival benefits except 1-year survival rate to patients with LA/MPC.
靶向治疗已为多种实体瘤患者带来了巨大的临床益处，但其对局部晚期/转移性胰腺癌（LA/MPC）患者的疗效存在争议。本系统评价比较了吉西他滨联合靶向药物（GEM + TA）与吉西他滨单药治疗或联合安慰剂（GEM ± PLC）在LA/MPC患者中的疗效和安全性。
检索PubMed和EMBASE数据库，查找2013年4月30日或之前发表的相关随机对照试验。主要终点为总生存期（OS）和无进展生存期（PFS）；次要终点为1年生存率、客观缓解率（ORR）和毒性率（TRs），毒性率定义为3/4级不良事件的发生率。使用Review Manager 5.1.7进行系统评价。
系统评价共纳入10项随机对照试验，涉及3899例患者（2195例男性；平均年龄63.6岁）。结果显示，GEM + TA与GEM ± PLC在OS（风险比[HR] = 0.97 [P = 0.85]）、PFS（HR = 0.95 [P = 0.14]）或ORR（优势比[OR] = 0.95 [P = 0.69]）方面无显著差异。然而，观察到两组在1年生存率方面存在微小差异（OR = 0.80 [P = 0.05]）。两组在贫血、腹泻、恶心、中性粒细胞减少、血小板减少和呕吐的3/4级TRs方面无显著差异。然而，GEM + TA组3/4级皮疹的发生率显著更高（OR = 8.31 [P < 0.01]）。
基于本分析结果，在吉西他滨治疗方案中添加靶向药物除了提高1年生存率外，并未给LA/MPC患者带来生存益处。
