Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
JAMA Oncol. 2020 May 1;6(5):e196828. doi: 10.1001/jamaoncol.2019.6828. Epub 2020 May 14.
Few clinical trials have been specifically designed for elderly patients with advanced non-small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit.
To determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC.
DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019.
Patients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks.
The primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model.
Of the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n = 217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n = 216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority = .003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed.
Carboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.
University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460.
重要性：专门针对晚期非小细胞肺癌（NSCLC）老年患者的临床试验较少，预计此类患者数量的增加促使人们寻找提供更大姑息治疗益处的新治疗选择。
目的：确定卡铂联合培美曲塞治疗后培美曲塞维持治疗与多西他赛单药治疗相比，在晚期非鳞状 NSCLC 老年患者中的总生存期（OS）方面是否不劣效。
设计、地点和参与者：这是一项在日本 79 家机构进行的开放性、多中心、非劣效性 3 期随机临床试验。纳入了无细胞毒性化疗史、东部合作肿瘤组体力状态 0 或 1、年龄 75 岁或以上的晚期非鳞状 NSCLC 患者。患者于 2013 年 8 月至 2017 年 2 月间入组，数据分析于 2018 年 11 月至 2019 年 2 月进行。
干预措施：患者随机接受多西他赛单药治疗（60mg/m2）每 3 周或 4 个周期卡铂（曲线下面积 5）联合培美曲塞（500mg/m2）每 3 周治疗，然后给予相同剂量培美曲塞维持治疗 3 周。
主要结局和测量：主要终点是 OS，采用意向治疗进行分析，95%CI 上限的 HR 的非劣效性边界为 1.154，采用分层 Cox 回归模型估计。
结果：433 名入组患者中，250 名（57.7%）为男性，中位（范围）年龄为 78（75-88）岁。在多西他赛组（n=217）中位 OS 为 15.5 个月（95%CI，13.6-18.4），卡铂-培美曲塞组（n=216）中位 OS 为 18.7 个月（95%CI，16.0-21.9），OS 的分层 HR 为 0.850（95%CI，0.684-1.056；P 非劣效性=0.003）。无进展生存期也更长在卡铂-培美曲塞组（未分层 HR，0.739；95%CI，0.609-0.896）。与多西他赛组相比，卡铂-培美曲塞组白细胞减少症（60/214[28.0%] vs 147/214[68.7%]）和中性粒细胞减少症（99/214[46.3%] vs 184/214[86.0%]）、发热性中性粒细胞减少症（9/214[4.2%] vs 38/214[17.8%]）和血小板减少症（55/214[25.7%] vs 3/214[1.4%]）和贫血症（63/214[29.4%] vs 4/214[1.9%]）的 3 或 4 级发生率较低，剂量减少的频率较低。
结论和相关性：卡铂-培美曲塞治疗后培美曲塞维持治疗是晚期非鳞状 NSCLC 老年患者一线治疗的有效选择。
试验注册：大学医院医疗信息网络临床试验注册处标识符：UMIN000011460。
