Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients
Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients
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DOI：
10.1016/j.jtho.2018.04.025
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发表时间：
2018-08-01
影响因子：
20.4
通讯作者：
de Marinis, Filippo
中科院分区：
文献类型：
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作者：
Garassino, Marina Chiara;Gelibter, Alain Jonathan;de Marinis, Filippo
前言：nivolumab是第一个被批准用于治疗非鳞状NSCLC的检查点抑制剂。我们报告了针对从不吸烟者和EGFR突变的非鳞状细胞肺癌患者的nivolumab意大利扩展接入计划的结果。方法：根据医生的要求，对IIIB/IV期非鳞状细胞肺癌患者进行一次或多次系统治疗后复发的患者使用nivolumab(每2周静脉注射3 mg/kg)。结果：在1588例非鳞状NSCLC患者中，305例(19.2%)从不吸烟。有1395名患者获得了EGFR状态。在102例(6.4%)EGFR突变阳性肿瘤患者中，51例(50%)从不吸烟。野生型表皮生长因子受体患者的客观应答率显著高于表皮生长因子受体突变肿瘤患者(19.6%比8.8%[p=0.007])，既往吸烟者和现在吸烟者明显高于不吸烟者(21.5%比9.2%[p=0.0001])，从不吸烟者的野生型表皮生长因子受体患者明显高于不吸烟者(11.0%比1.9%[p=0.0001])。携带野生型EGFR的吸烟者和携带突变的EGFR吸烟者的客观有效率差异无统计学意义(22.0%对20.6%)。中位无进展存活率或中位总存活率在统计学上没有显著差异。EGFR野生型肿瘤患者的中位总生存期为11个月，EGFR突变型肿瘤患者为8.3个月，吸烟者为11.6个月，不吸烟者为10.0个月，不吸烟者为11.0个月，不吸烟者为5.6个月。患有EGFR突变肿瘤的吸烟者为14.1个月，而患有EGFR野生型肿瘤的吸烟者为11.3个月。结论：意大利非鳞状NSCLC人群扩大准入计划的数据表明，根据患者的EGFR突变状态和吸烟习惯，患者亚组可能从nivolumab中受益不同。这些结果值得进一步调查。(C)2018年国际肺癌研究协会。爱思唯尔公司出版，版权所有。
Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC.Methods: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab.Results: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors.Conclusions: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.