Yang James Chih-Hsin, Kang Jin Hyoung, Mok Tony, Ahn Myung-Ju, Srimuninnimit Vichien, Lin Chia-Chi, Kim Dong-Wan, Tsai Chun-Ming, Barraclough Helen, Altug Sedat, Orlando Mauro, Park Keunchil
National Taiwan University Hospital, Taipei, Taiwan.
The Catholic University of Korea, St. Mary's Hospital, Seoul, Republic of Korea.
Eur J Cancer. 2014 Sep;50(13):2219-30. doi: 10.1016/j.ejca.2014.05.011. Epub 2014 Jun 18.
In the Iressa Pan-ASia Study (IPASS), gefitinib claimed improved progression-free survival (PFS) versus carboplatin-paclitaxel in clinically selected lung cancer patients. The primary objective of this study was to assess the PFS of pemetrexed-cisplatin (PC) followed by gefitinib maintenance versus gefitinib monotherapy in an IPASS-like population.
In this open-label, randomised, phase 3 trial, eligible patients were ⩾18 years, chemonaïve, East Asian, light ex-smokers/never-smokers with advanced non-squamous non-small cell lung cancer, an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and unknown epidermal growth factor receptor (EGFR) mutation status who enrolled at 12 sites in Asia. Patients randomly received (1:1) pemetrexed (500 mg/m(2)) plus cisplatin (75mg/m(2)) for six 21-day cycles, followed by gefitinib maintenance or gefitinib monotherapy (250 mg/day). Patient tissue was retrospectively analysed for EGFR mutations. This study is registered with ClinicalTrials.gov, NCT01017874.
Between 23rd November 2009 and 27th April 2012, 253 patients entered, and 236 patients were randomly assigned to and treated with PC therapy (N=114) and gefitinib monotherapy (N=118). Between-arm baseline characteristics were balanced. PFS was not significantly different between treatment arms (p=0.217). The unadjusted hazard ratio (HR) was 0.85 (95% confidence interval (CI) 0.63-1.13). The HR should be cautiously interpreted as it was not constant. EGFR mutation status was determined for 74 tissue samples; 50 (67.6%) had mutations. In a pre-specified subgroup analysis, only the treatment-by-EGFR mutation interaction was significant (p=0.008) for PFS. For the entire treatment period, a higher proportion of patients in the PC/gefitinib arm versus gefitinib experienced possibly drug-related grade 3-4 treatment-emergent adverse events (39 of 114 [34%] versus 19 of 118 [16%]; p=0.002).
In the intention-to-treat (ITT) population, PFS was not significantly different. In the biomarker-assessable population, front-line EGFR tyrosine kinase inhibitor monotherapy was not efficacious in patients with wild-type EGFR. Identification of EGFR mutation status is key in the management of advanced non-squamous non-small cell lung cancer.
Eli Lilly and Company.
在易瑞沙泛亚洲研究（IPASS）中，在临床选择的肺癌患者中，吉非替尼的无进展生存期（PFS）相较于卡铂-紫杉醇有所改善。本研究的主要目的是在IPASS类似人群中评估培美曲塞-顺铂（PC）序贯吉非替尼维持治疗与吉非替尼单药治疗的PFS。
在这项开放标签、随机、3期试验中，符合条件的患者年龄≥18岁，未接受过化疗，为东亚地区轻度既往吸烟者/从不吸烟者，患有晚期非鳞状非小细胞肺癌，东部肿瘤协作组（ECOG）体能状态为0 - 1，且表皮生长因子受体（EGFR）突变状态未知，在亚洲的12个地点入组。患者随机接受（1:1）培美曲塞（500 mg/m²）加顺铂（75mg/m²），共六个21天周期，随后接受吉非替尼维持治疗或吉非替尼单药治疗（250 mg/天）。对患者组织进行回顾性EGFR突变分析。本研究已在ClinicalTrials.gov注册，编号为NCT01017874。
在2009年11月23日至2012年4月27日期间，253例患者入组，236例患者被随机分配并接受PC治疗（N = 114）和吉非替尼单药治疗（N = 118）。组间基线特征均衡。治疗组之间的PFS无显著差异（p = 0.217）。未调整的风险比（HR）为0.85（95%置信区间（CI）0.63 - 1.13）。由于HR不恒定，应谨慎解读。对74份组织样本进行了EGFR突变状态检测；50份（67.6%）有突变。在预先设定的亚组分析中，仅治疗与EGFR突变的相互作用对PFS具有显著意义（p = 0.008）。在整个治疗期间，PC/吉非替尼组与吉非替尼组相比，有更高比例的患者经历了可能与药物相关的3 - 4级治疗中出现的不良事件（114例中的39例[34%]对118例中的19例[16%]；p = 0.002）。
在意向性治疗（ITT）人群中，PFS无显著差异。在生物标志物可评估人群中，一线EGFR酪氨酸激酶抑制剂单药治疗对野生型EGFR患者无效。确定EGFR突变状态是晚期非鳞状非小细胞肺癌管理的关键。
礼来公司。
