2014年ASCO大会中的肺癌重点壁报会场中，一项研究探讨在ALK阳性非鳞非小细胞肺癌（NSCLC）患者中，一线
背景：
口服ALK抑制剂克唑替尼一线治疗晚期ALK阳性NSCLC，相比于标准化疗方案的疗效还未知。一项多中心、随机、开放标签的III期研究比较了在此情况下，克唑替尼对比培美曲塞-铂类化疗（PPC）的疗效和安全性。
方法：
从2011年1月到2013年7月，343名未治的晚期非鳞ALK阳性NSCLC患者随机（1:1）分配到克唑替尼组（250mg PO BID；n=172）或者PPC组（培美曲塞 500mg/m2 +顺铂 75mg/m2或者卡铂 AUC 5-6；所有都是IV q3w,≤6周期；n=171）。克唑替尼组或PPC组在PD后可分别持续克唑替尼或交叉为克唑替尼。主要终点是PFS，次要终点包括ORR，OS，安全性，病人报告结局。
结果：
克唑替尼和PPC组每种分层的比例如下：亚洲人45%和47%；ECOG PS 0/1 94%和95%；既往治疗过脑转移26%和28%。该研究达到了主要终点，即在延长PFS上克唑替尼优于PPC（10.9 vs. 7.0 个月; HR: 0.454; 95% CI: 0.346−0.596; P<0.0001）。克唑替尼的ORR也明显较高（74% vs. 45%; P<0.0001）。68%的病人仍在随访中，目前未发现OS的统计学差异（HR: 0.821; 95% CI: 0.536−1.255; P=0.1804）。在数据截止期，109名PPC组的病人交叉至克唑替尼组。
克唑替尼和PPC组的不良事件与既往报道过的一致。克唑替尼最常见的不良事件为
结论：
一线克唑替尼相比于标准化疗带来PFS和ORR的明显改善，安全性可接受。这些发现建立了克唑替尼作为既往未经治疗的晚期ALK阳性非鳞状NSCLC的标准治疗。临床试验信息：2010-021336-33。
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会议专题》》》2014年ASCO年会专题报道
阅读摘要原文
First-line crizotinib versus pemetrexed–cisplatin or pemetrexed–carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014)(Abstract No:8002)
Author(s): Tony Mok, Dong-Wan Kim, Yi-Long Wu, et al.
Type: Poster Highlights Session
Background: The efficacy of the oral ALK inhibitor crizotinib as 1st-line treatment for advanced ALK-positive NSCLC compared with standard chemotherapy is unknown. A multicenter, randomized open-label phase III study was conducted to compare the efficacy and safety of crizotinib vs. pemetrexed–platinum chemotherapy (PPC) in this setting.
Methods: Between Jan 2011 and Jul 2013, 343 pts with previously untreated advanced non-squamous ALK-positive NSCLC were randomized 1:1 to receive crizotinib 250 mg PO BID (n=172) or PPC (pemetrexed 500 mg/m2 + either cisplatin 75 mg/m2 or carboplatin AUC 5–6; all IV q3w for ≤6 cycles; n=171). Continuation of/crossover to crizotinib after PD (per independent radiologic review) was allowed for pts randomized to crizotinib or PPC, respectively. The primary endpoint was PFS. Secondary endpoints included ORR, OS, safety, and pt-reported outcomes.
Results: Proportions of pts in the crizotinib and PPC treatment groups with each stratification factor were 45% and 47% Asians, 94% and 95% with ECOG PS 0/1, and 26% and 28% with previously treated brain metastases, respectively. The study met its primary objective, demonstrating superiority of crizotinib over PPC in prolonging PFS (median 10.9 vs. 7.0 mo; HR: 0.454; 95% CI: 0.346−0.596; P<0.0001). The ORR was significantly higher with crizotinib (74% vs. 45%; P<0.0001). With 68% of pts still in follow-up, a statistically significant improvement in OS was not demonstrated (HR: 0.821; 95% CI: 0.536−1.255; P=0.1804). At time of data cut-off 109 pts on PPC had crossed over to crizotinib. AEs with crizotinib and PPC were consistent with those previously reported in patients with advanced ALK-positive or unselected NSCLC, respectively. The most common all-causality AEs with crizotinib were vision disorder and GI symptoms.
Conclusions: First-line crizotinib treatment showed significant improvements in PFS and ORR compared with standard chemotherapy and had an acceptable safety profile. These findings establish crizotinib as the standard of care for pts with previously untreated advanced ALK-positive non-squamous NSCLC. Clinical trial information: 2010-021336-33.
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