Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
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DOI：
10.1200/jco.2017.76.8390
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发表时间：
2018-09-01
影响因子：
45.3
通讯作者：
Perrone, Francesco
中科院分区：
文献类型：
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作者：
Gridelli, Cesare;Morabito, Alessandro;Perrone, Francesco
目的通过对两个平行的III期试验Miles-3和Miles-4的联合分析，验证在老年晚期非小细胞肺癌(NSCLC)一线治疗中加用顺铂的疗效。在每个试验中，需要382个事件来检测死亡的风险比(HR)为0.75，功率为80%，双尾为0.05。由于进展缓慢，试验提前结束，但联合数据库允许我们根据治疗意向分析顺铂的疗效，并通过试验、组织类型、非铂类辅助药物、阶段、表现状态、性别、年龄和研究中心的大小进行调整。结果从2011年3月到2016年8月，531名患者(Miles-3,299；Miles-4,232)被分配到吉西他滨或培美曲塞而不使用顺铂(n=268)或使用顺铂(n=263)。中位年龄为75岁，79%为男性，70%为非鳞状组织病。在中位数2年的随访中，记录了384例死亡和448例无进展生存事件。顺铂对总生存期无明显延长作用(HR，0.86；95%CI，0.70~1.05；P=.14)，总体健康状况生活质量评分未见改善，但无进展生存率(HR，0.76；95%CI，0.63~0.92；P=.005)和客观有效率(15.5%对8.5%；P=.02)显著改善。结论在单药化疗的基础上加用顺铂并不能显著延长晚期非小细胞肺癌患者的总体生存时间，也不能改善老年晚期非小细胞肺癌患者的总体健康状况和生活质量评分。
PurposeTo test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4.Patients and MethodsPatients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center.ResultsFrom March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin.ConclusionThe addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.