Kenmotsu Hirotsugu, Yamamoto Nobuyuki, Yamanaka Takeharu, Yoshiya Katsuo, Takahashi Toshiaki, Ueno Tsuyoshi, Goto Koichi, Daga Haruko, Ikeda Norihiko, Sugio Kenji, Seto Takashi, Toyooka Shinichi, Date Hiroshi, Mitsudomi Tetsuya, Okamoto Isamu, Yokoi Kohei, Saka Hideo, Okamoto Hiroaki, Takiguchi Yuichi, Tsuboi Masahiro
Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho Sunto-gun, Japan.
Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
J Clin Oncol. 2020 Jul 1;38(19):2187-2196. doi: 10.1200/JCO.19.02674. Epub 2020 May 14.
To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non-small-cell lung cancer (NSCLC).
We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive either pemetrexed (500 mg/m, day 1) plus cisplatin (75 mg/m, day 1) or vinorelbine (25 mg/m, days 1 and 8) plus cisplatin (80 mg/m, day 1) with stratification by sex, age, pathologic stage, mutation, and institution. These treatments were planned to be given every 3 weeks for 4 cycles. The primary end point was recurrence-free survival in the modified intent-to-treat population, excluding ineligible patients.
Between March 2012 and August 2016, 804 patients were enrolled (402 assigned to vinorelbine plus cisplatin and 402 assigned to pemetrexed plus cisplatin). Of 784 eligible patients, 410 (52%) had stage IIIA disease and 192 (24%) had -sensitive mutations. At a median follow-up of 45.2 months, median recurrence-free survival was 37.3 months for vinorelbine plus cisplatin and 38.9 months for pemetrexed plus cisplatin, with a hazard ratio of 0.98 (95% CI, 0.81 to 1.20; 1-sided = .474). Grade 3-4 toxicities reported more frequently for vinorelbine plus cisplatin than for pemetrexed plus cisplatin were febrile neutropenia (11.6% 0.3%, respectively), neutropenia (81.1% 22.7%, respectively), and anemia (9.3% 2.8%, respectively). One treatment-related death occurred in each arm.
Although this study failed to show the superiority of pemetrexed plus cisplatin for patients with resected nonsquamous NSCLC, this regimen showed a better tolerability as adjuvant chemotherapy.
评估培美曲塞联合顺铂与长春瑞滨联合顺铂作为术后辅助化疗方案用于病理分期为II-IIIA期非鳞状非小细胞肺癌（NSCLC）患者的疗效。
我们在日本7个临床研究组的50家机构开展了一项随机、开放标签的III期研究。将完全切除的病理分期为II-IIIA期（TNM第7版）的非鳞状NSCLC患者随机分配接受培美曲塞（500mg/m²，第1天）联合顺铂（75mg/m²，第1天）或长春瑞滨（25mg/m²，第1天和第8天）联合顺铂（80mg/m²，第1天）治疗，并根据性别、年龄、病理分期、基因突变和机构进行分层。这些治疗计划每3周进行1次，共4个周期。主要终点是在意向性分析人群（不包括不符合条件的患者）中的无复发生存期。
2012年3月至2016年8月期间，共入组804例患者（402例分配至长春瑞滨联合顺铂组，402例分配至培美曲塞联合顺铂组）。在784例符合条件的患者中，410例（52%）为IIIA期疾病，192例（24%）有敏感基因突变。中位随访45.2个月时，长春瑞滨联合顺铂组的中位无复发生存期为37.3个月，培美曲塞联合顺铂组为38.9个月，风险比为0.98（95%CI，0.81至1.20；单侧P = 0.474）。长春瑞滨联合顺铂组比培美曲塞联合顺铂组更频繁报告的3-4级毒性反应为发热性中性粒细胞减少（分别为11.6%对0.3%）、中性粒细胞减少（分别为81.1%对22.7%）和贫血（分别为9.3%对2.8%）。每组均发生1例与治疗相关的死亡。
尽管本研究未能显示培美曲塞联合顺铂用于切除的非鳞状NSCLC患者的优越性，但该方案作为辅助化疗耐受性更好。
