Phase III Trial of Bevacizumab in Combination With Gemcitabine and Erlotinib in Patients With Metastatic Pancreatic Cancer
Phase III Trial of Bevacizumab in Combination With Gemcitabine and Erlotinib in Patients With Metastatic Pancreatic Cancer
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DOI：
10.1200/jco.2008.20.0238
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发表时间：
2009-05-01
影响因子：
45.3
通讯作者：
Moore, Malcolm J.
中科院分区：
文献类型：
--
作者：
Van Cutsem, Eric;Vervenne, Walter L.;Moore, Malcolm J.
目的
吉西他滨治疗对转移性胰腺癌患者有一定益处。在吉西他滨基础上加用厄洛替尼相较于单用吉西他滨，总生存期（OS）有小幅但显著的改善。贝伐珠单抗联合吉西他滨的II期研究结果为吉西他滨 - 厄洛替尼加用贝伐珠单抗或安慰剂的III期试验提供了理论依据。
患者与方法
在这项双盲III期试验中，转移性胰腺腺癌患者被随机分配接受吉西他滨（1000mg/m²/周）、厄洛替尼（100mg/天）和贝伐珠单抗（5mg/kg，每2周一次），或吉西他滨、厄洛替尼和安慰剂。主要终点是总生存期；次要终点包括无进展生存期（PFS）、疾病控制率和安全性。
结果
共有301名患者被随机分配到安慰剂组，306名患者被分配到贝伐珠单抗组。贝伐珠单抗组和安慰剂组的中位总生存期分别为7.1个月和6.0个月（风险比[HR]，0.89；95%置信区间，0.74 - 1.07；P = 0.2087）；该差异无统计学意义。在吉西他滨 - 厄洛替尼基础上加用贝伐珠单抗显著改善了无进展生存期（HR，0.73；95%置信区间，0.61 - 0.86；P = 0.0002）。贝伐珠单抗加吉西他滨 - 厄洛替尼治疗耐受性良好：安全性数据与先前描述的各药物的安全性特征无差异。
结论
主要目标未达成。在吉西他滨 - 厄洛替尼基础上加用贝伐珠单抗未使转移性胰腺癌患者的总生存期有统计学上的显著改善。然而，与安慰剂相比，贝伐珠单抗组的无进展生存期显著更长。在吉西他滨 - 厄洛替尼基础上加用贝伐珠单抗未观察到意外的安全性事件。
PurposeTreatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo.Patients and MethodsPatients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase III trial. Primary end point was OS; secondary end points included progression-free survival (PFS), disease control rate, and safety.ResultsA total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087); this difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved PFS (HR, 0.73; 95% CI, 0.61 to 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs.ConclusionThe primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib.