Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer
Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2016.66.9861
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发表时间：
2016-09-01
影响因子：
45.3
通讯作者：
Antonia, Scott
中科院分区：
文献类型：
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作者：
Rizvi, Naiyer A.;Hellmann, Matthew D.;Antonia, Scott
enivolumab是一种全人免疫球蛋白G4程序性死亡-1免疫检查点抑制剂抗体，已证明可改善先前治疗的晚期非小细胞肺癌（NSCLC）患者的生存率。CheckMate 012是一项I期多队列研究，旨在探索nivolumab作为单一疗法或与当前标准疗法联合治疗一线晚期NSCLC的安全性和有效性。在这里，我们报告了纳武单抗加铂基双重化疗（PT-DC）的结果。患者和方法患者（N = 56）每3周接受纳武单抗（静脉注射）加PT-DC同时治疗，共4个周期，随后单独使用纳武单抗，直到进展或不可接受的毒性。方案为纳武单抗10mg /kg +吉西他滨-顺铂（鳞状）或培美曲塞-顺铂（非鳞状）或纳武单抗5或10mg /kg +紫杉醇-卡铂（所有组织学）。主要目的是评估安全性和耐受性。次要目标包括客观缓解率和24周无进展生存率（根据实体肿瘤反应评价标准1.1版）；探索目标包括总生存期（OS）和肿瘤程序性死亡配体-1表达的反应。结果治疗前6周未发生剂量限制性毒性反应。45%的患者（56例患者中的25例）报告了3级或4级治疗相关不良事件（ae）；7%的患者（n = 4）患有肺炎。21%的患者（n = 12）由于治疗相关的不良事件而停止了所有的研究治疗。纳武单抗10mg /kg +吉西他滨-顺铂、纳武单抗10mg /kg +培美曲塞-顺铂、纳武单抗10mg /kg +紫杉醇-卡铂和纳武单抗5mg /kg +紫杉醇-卡铂的客观有效率分别为33%、47%、47%和43%；24周无进展生存率分别为51%、71%、38%和51%；2年生存率分别为25%、33%、27%和62%。无论肿瘤程序性死亡配体-1表达与否，均能实现应答。结论：纳武单抗联合PT-DC的安全性与单个药物的预期一致；然而，与ae相关的治疗中断与联合用药更大。观察到令人鼓舞的活性，特别是纳沃单抗5 mg/kg加紫杉醇-卡铂组，2年总生存率为62%。(C) 2016年由美国临床肿瘤学会出版
PurposeNivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).Patients and MethodsPatients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progressionfree survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression.ResultsNo dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression.ConclusionThe safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%. (C) 2016 by American Society of Clinical Oncology