Kinki University School of Medicine, Osaka, Japan.
J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235. Epub 2011 Jun 13.
The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status.
In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS.
OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09).
EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation-positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.
先前发表了比较吉非替尼与卡铂/紫杉醇在未经治疗的从不吸烟和轻度吸烟的晚期肺腺癌患者中的疗效的 Iressa 泛亚研究（IPASS）的结果。本报告根据表皮生长因子受体（EGFR）生物标志物状态介绍总生存期（OS）和疗效。
共有 1217 名患者被随机分配。分析的生物标志物为 EGFR 突变（扩增突变难治系统；437 名可评估患者）、EGFR 基因拷贝数（荧光原位杂交；406 名可评估患者）和 EGFR 蛋白表达（免疫组化；365 名可评估患者）。OS 分析在 78%成熟度时进行。使用 Cox 比例风险模型按无进展生存期（PFS）和 OS 的随机分配治疗相互作用评估生物标志物状态。
吉非替尼与卡铂/紫杉醇的 OS（954 例死亡）相似，总体治疗之间无显著差异（风险比[HR]，0.90；95%CI，0.79 至 1.02；P =.109）或在 EGFR 突变阳性（HR，1.00；95%CI，0.76 至 1.33；P =.990）或 EGFR 突变阴性（HR，1.18；95%CI，0.86 至 1.63；P =.309；治疗与 EGFR 突变相互作用 P =.480）亚组。随机分配至卡铂/紫杉醇的 EGFR 突变阳性患者中，有很大比例（64.3%）接受了后续的 EGFR 酪氨酸激酶抑制剂治疗。对于肿瘤同时具有高 EGFR 基因拷贝数和 EGFR 突变的患者，吉非替尼的 PFS 显著延长（HR，0.48；95%CI，0.34 至 0.67），但当高 EGFR 基因拷贝数不伴有 EGFR 突变时 PFS 显著缩短（HR，3.85；95%CI，2.09 至 7.09）。
EGFR 突变是预测 PFS 和肿瘤对一线吉非替尼与卡铂/紫杉醇反应的最强生物标志物。EGFR 基因拷贝数的预测价值由共存的 EGFR 突变驱动（事后分析）。在 EGFR 突变阳性亚组中观察到的与 PFS 相关的治疗差异在 OS 中并不明显。OS 结果可能因大量患者交叉到替代治疗而受到混淆。
