Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial
Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial
复制标题
DOI：
10.1016/s1470-2045(12)70063-3
复制
发表时间：
2012-03-01
期刊：
影响因子：
51.1
通讯作者：
Gridelli, Cesare
中科院分区：
文献类型：
--
作者：
Paz-Ares, Luis;de Marinis, Filippo;Gridelli, Cesare
背景 晚期非鳞状非小细胞肺癌 (NSCLC) 患者在使用含铂非培美曲塞双药诱导治疗后可受益于培美曲塞维持治疗。 PARAMOUNT 试验研究了培美曲塞继续维持治疗是否能改善培美曲塞联合顺铂诱导治疗后的无进展生存期。 方法 在这项双盲、多中心、3 期、随机安慰剂对照试验中，晚期非鳞状 NSCLC 患者年龄为 18 岁或以上，既往未接受过肺癌全身化疗，至少有一个可测量的病变，并且具有东部肿瘤合作组 (ECOG) 表现状态为 0 或 1 参与。随机化之前，患者进入诱导阶段，包括四个周期的诱导培美曲塞 (500 mg/m(2)) 加顺铂 (75 mg/m(2))（21 天周期的第一天）。完成四个诱导周期后未进展且 ECOG 体力状态为 0 或 1 的患者根据疾病分期（IIIB 或 IV）、ECOG 体力状态（0 或 1）和诱导反应（完全或部分反应，或疾病稳定）进行分层，并随机分配（2:1 比例）接受培美曲塞（500 mg/m(2) 每 21 天）维持治疗加最佳支持治疗或安慰剂加最佳支持治疗直至疾病发生进展。使用 Pocock 和 Simon 最小化方法进行随机化。患者和研究人员对治疗分配情况不知情。主要终点是意向治疗人群的无进展生存期。这项研究已在 ClinicalTrials.gov 注册，NCT00789373。结果 在纳入的 1022 名患者中，939 名患者参与了诱导阶段。其中，539 名患者被随机分配接受培美曲塞加最佳支持治疗（n=359）或安慰剂加最佳支持治疗（n=180）的持续维持治疗。在 359 名随机接受培美曲塞继续维持治疗的患者中，与安慰剂组相比，疾病进展的风险显着降低（HR 0.62，95% CI 0.49-0.79；p
Background Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin.Methods In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2: 1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m(2) every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00789373.Findings Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0.62, 95% CI 0.49-0.79; p