Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial.
Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial.
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DOI：
10.1186/2162-3619-3-26
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发表时间：
2014
影响因子：
10.9
通讯作者：
Johnson DH
中科院分区：
文献类型：
--
作者：
Moran T;Felip E;Keedy V;Borghaei H;Shepherd FA;Insa A;Brown H;Fitzgerald T;Sathyanarayanan S;Reilly JF;Mauro D;Hsu K;Yan L;Johnson DH
我们在20例难治性晚期非小细胞肺癌（NSCLC）患者中进行了一项I/II期序贯试验，研究了dalotuzumab（一种选择性抗胰岛素生长因子1受体单克隆抗体（IGF 1 R MoAb））联合厄洛替尼的安全性和抗肿瘤活性。II期试验比较了单独厄洛替尼和厄洛替尼加达妥珠单抗（在I期试验中确定的mg/kg）的结果。150 mg厄洛替尼加10 mg/kg dalotuzumab是安全的。II期试验包括厄洛替尼组37例患者和厄洛替尼+dalotuzumab组38例患者，无进展生存期分别为1.6和2.5个月，总生存期分别为10.2和6.6个月，客观缓解率分别为7.9%和2.7%，两组之间无显著差异。3-5级不良事件分别发生在11例（28.9%）和13例（35.1%）患者中。最常见的不良事件是虚弱（36.8% vs. 37.8%）、脱水（5.3% vs. 2.7%）、腹泻（71% vs. 81.1%）、高血糖（13.1% vs. 18.9%）和皮肤相关毒性（92.1% vs. 86.4%）。在厄洛替尼基础上加用dalotuzumab并不能改善难治性晚期NSCLC患者的疗效结局。
We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial. Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 13 (35.1%) patients, respectively. The most frequent adverse events were asthenia (36.8% vs. 37.8%), dehydration (5.3% vs. 2.7%), diarrhea (71% vs. 81.1%), hyperglycemia (13.1% vs.18.9%), and skin-related toxicities (92.1% vs. 86.4%). The addition of dalotuzumab to erlotinib did not improve efficacy outcome in patients with refractory advanced NSCLC.