Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China.
Medical Oncology Division, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama City, Osaka 589 8511, Japan.
Lung Cancer. 2017 Feb;104:119-125. doi: 10.1016/j.lungcan.2016.11.022. Epub 2016 Nov 30.
The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC.
Eligible patients (aged ≥18 years; histologically/cytologically confirmed Stage IIB/IV adenocarcinoma NSCLC; non- or former light-smokers; treatment-naïve) were randomly assigned 1:1 to gefitinib (250mg/day) or carboplatin (dose calculated to produce an area under the curve of 5 or 6 mg/mL/minute)/paclitaxel (200mg/m). Primary endpoint: PFS. BICR analyses included PFS, ORR, and duration of response (DoR).
Scans from 186 IPASS patients (gefitinib n=88, carboplatin/paclitaxel n=98) with EGFR mutation-positive NSCLC were available for BICR. Consistent with investigator-assessed results, in patients with EGFR mutation-positive NSCLC: PFS (hazard ratio 0.54; 95% confidence interval [CI] 0.38, 0.79; p=0.0012) and ORR (odds ratio 3.00; 95% CI 1.63, 5.54; p=0.0004) were significantly longer with gefitinib versus carboplatin/paclitaxel. The median DoR by BICR was 9.6 months with gefitinib and 5.5 months with carboplatin/paclitaxel.
BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy.
III 期、随机、开放标签 IPASS 研究（NCT00322452）比较了一线表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKI）吉非替尼与卡铂/紫杉醇用于亚洲晚期非小细胞肺癌（NSCLC）患者，结果显示，接受吉非替尼治疗的 EGFR 突变阳性 NSCLC 患者与 EGFR 突变阴性 NSCLC 患者相比，研究者评估的无进展生存期（PFS）和客观缓解率（ORR）显著延长。我们报告了美国 FDA 要求的 IPASS 数据的事后分析，该分析是对 EGFR 突变阳性 NSCLC 患者亚组进行的盲法独立中央审查（BICR）。
符合条件的患者（年龄≥18 岁；组织学/细胞学证实的 IIB/IV 期腺癌 NSCLC；非吸烟者或曾经轻度吸烟者；初治）按 1:1 随机分配至吉非替尼（250mg/天）或卡铂（剂量计算为产生 5 或 6mg/mL/min 的曲线下面积）/紫杉醇（200mg/m）。主要终点：PFS。BICR 分析包括 PFS、ORR 和缓解持续时间（DoR）。
186 例 EGFR 突变阳性 NSCLC 患者的 IPASS 扫描结果可用于 BICR（吉非替尼 n=88，卡铂/紫杉醇 n=98）。与研究者评估的结果一致，在 EGFR 突变阳性 NSCLC 患者中：吉非替尼与卡铂/紫杉醇相比，PFS（风险比 0.54；95%置信区间 [CI] 0.38, 0.79；p=0.0012）和 ORR（优势比 3.00；95% CI 1.63, 5.54；p=0.0004）显著延长。BICR 评估的中位 DoR 为吉非替尼 9.6 个月，卡铂/紫杉醇为 5.5 个月。
BICR 分析支持 IPASS 数据的原始研究者评估结果。EGFR 突变阳性状态仍然是对一线 TKI 治疗有反应的重要预测因素。
