SCI
21 Apr 2020
Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non–Small Cell Lung Cancer
Rizvi Naiyer A,Cho Byoung Chul,Reinmuth Niels et al. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial.[J] .JAMA Oncol, 2020, undefined: undefined.
IMPORTANCE 重要性
Checkpoint inhibitors targeting programmed cell death 1 or its ligand (PD-L1) as monotherapies or in combination with anti–cytotoxic T-lymphocyte–associated antigen 4 ave shown clinical activity in patients with metastatic non–small cell lung cancer.
靶向程序性死亡1或其配体（PD-L1）作为单一疗法或与抗细胞毒性T淋巴细胞相关抗原4结合使用的Checkpoint抑制剂在转移性非小细胞肺癌患者中表现出临床活性。
OBJECTIVE 目的
To compare durvalumab, with or without tremelimumab, with chemotherapy as a first-line treatment for patients with metastatic non–small cell lung cancer.
Durvalumab联合Tremelimumab或不联合曲美莫单抗与标准化学治疗一线治疗转移性非小细胞肺癌的效果
DESIGN, SETTING, AND PARTICIPANTS 设计，设置和参与者
This open-label, phase 3 randomized clinicaltrial (MYSTIC) was conducted at 203 cancer treatment centers in 17 countries. Patients with treatment-naive, metastatic non–small cell lung cancer who had no sensitizing EGFR or ALK genetic alterations were randomized to receive treatment with durvalumab, durvalumab plus tremelimumab, or chemotherapy. Data were collected from July 21, 2015, to October 30, 2018.
这项开放标签的3期随机临床试验（MYSTIC）在17个国家/地区的203个癌症治疗中心进行。没有敏感EGFR或ALK基因改变的初治转移性非小细胞肺癌患者被随机分配接受durvalumab，durvalumab联合tremelimumab或化疗的治疗。数据收集时间为2015年7月21日至2018年10月30日。
INTERVENTIONS 干预措施
Patients were randomized (1:1:1) to receive treatment with durvalumab (20 mg/kg every 4 weeks), durvalumab (20 mg/kg every 4 weeks) plus tremelimumab (1 mg/kg every 4 weeks, up to 4 doses), or platinum-based doublet chemotherapy.
患者被随机（1：1：1）接受durvalumab（每4周20 mg / kg），durvalumab（每4周20 mg / kg）和tremelimumab（每4周1 mg / kg）的治疗，最多4剂 ），或铂类双药化疗。
MAIN OUTCOMES AND MEASURES 主要成果和措施
The primary end points, assessed in patients with 25% of tumor cells expressing PD-L1, were overall survival (OS) for durvalumab vs chemotherapy, and OS and progression-free survival (PFS) for durvalumab plus tremelimumab vs chemotherapy. Analysis of blood tumor mutational burden (bTMB) was exploratory.
在25％的表达PD-L1的肿瘤细胞的患者中评估的主要终点是durvalumab vs化疗的总生存期（OS），以及durvalumab联合tremelimumab vs化疗的OS和无进展生存期（PFS）。血液肿瘤突变负担（bTMB）的分析是探索性的。
RESULTS 结果
Between July 21, 2015, and June 8, 2016, 1118 patients were randomized. Baseline demographic and disease characteristics were balanced between treatment groups. Among 488 patients with 25% of tumor cells expressing PD-L1, median OS was 16.3 months with durvalumab vs 12.9 months with chemotherapy. Median OS was 11.9 months with durvalumab plus tremelimumab. Median PFS was 3.9 months with durvalumab plus tremelimumab vs 5.4 months with chemotherapy. Among 809 patients with evaluable bTMB, those with a bTMB 20 mutations per megabase showed improved OS for durvalumab plus tremelimumab vs chemotherapy vs 10.0 months;. Treatment-related adverse events of grade 3 or higher occurred in 55 (14.9%) of 369 patients who received treatment with durvalumab, 85 (22.9%) of 371 patients who received treatment with durvalumab plus tremelimumab, and 119 (33.8%) of 352 patients who received treatment with chemotherapy. These adverse events led to death in 2 (0.5%), 6 (1.6%), and 3 (0.9%) patients, respectively.
在2015年7月21日至2016年6月8日之间，随机分配了1118例患者。治疗组之间基线人口统计学和疾病特征是平衡的。在488名患者中，有25％的肿瘤细胞表达PD-L1，其中durvalumab的中位OS为16.3个月，而化疗为12.9个月。durvalumab加tremelimumab的中位OS为11.9个月。durvalumab加tremelimumab联合治疗的中位PFS为3.9个月，而化疗为5.4个月。在809位可评估bTMB的患者中，每兆碱基20个突变的bTMB患者显示durvalumab加tremelimumab的OS较化疗改善了10.0个月。接受durvalumab治疗的369例患者中有55（14.9％）发生了3级或更高的治疗相关不良事件，接受durvalumab加tremelimumab治疗的371例患者中有85（22.9％）以及352例中有119例（33.8％）接受化学疗法治疗的患者。这些不良事件分别导致2（0.5％），6（1.6％）和3（0.9％）例死亡。
CONCLUSIONS AND RELEVANCE 结论与关联
The phase 3 MYSTIC study did not meet its primary end points of improved OS with durvalumab vs chemotherapy or improved OS or PFS with durvalumab plus tremelimumab vs chemotherapy in patients with 25% of tumor cells expressing PD-L1. Exploratory analyses identified a bTMB threshold of 20 mutations per megabase for optimal OS benefit with durvalumab plus tremelimumab.
在25％的表达PD-L1肿瘤细胞的患者中，MYSTIC的3期研究未达到其相对于化疗而言改善的OS或相对于化疗而言改善的OS或PFS的方法。探索性分析确定了bTMB阈值为每兆碱基20个突变，以通过durvalumab和tremelimumab的最佳OS获益。
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