Phase II Study of Afatinib, an Irreversible ErbB Family Blocker, in EGFR FISH-Positive Non-Small-Cell Lung Cancer
Phase II Study of Afatinib, an Irreversible ErbB Family Blocker, in EGFR FISH-Positive Non-Small-Cell Lung Cancer
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DOI：
10.1097/jto.0000000000000442
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发表时间：
2015-04-01
影响因子：
20.4
通讯作者：
Santoro, Armando
中科院分区：
文献类型：
--
作者：
Cappuzzo, Federico;Finocchiaro, Giovanna;Santoro, Armando
简介：阿法替尼是一种口服不可逆ErbB家族阻滞剂，已证明其在表皮生长因子受体（EGFR）突变阳性晚期肺腺癌中的疗效和安全性。目前尚不清楚这种活性是否也发生在EGFR基因过表达的患者中，无论突变状态如何。这项II期研究调查了阿法替尼在晚期非小细胞肺癌中的活性和安全性，EGFR基因拷贝数增加和/或基因扩增通过荧光原位杂交（FISH），有或没有EGFR突变。方法：EGFR基因过表达通过FISH分析评估;高多体性或基因扩增的患者被认为是FISH阳性。患者每日接受≤ 50 mg阿法替尼（单药治疗）。终点包括客观反应率（ORR;主要），疾病控制率（DCR），无进展生存期（PFS），总生存期（OS），和safety.Results：筛选的223例患者中，69例FISH阳性，符合治疗资格标准。总体ORR为13.0%（n = 9/69）。在基因扩增（20.0%; n = 5/25）和EGFR突变阳性肿瘤（25.0%; n = 3/12）患者中观察到较高的ORR。总体DCR为50.7%（n = 35/69;中位持续时间：24.9周），在基因扩增患者中观察到较高的DCR 64.0%（n = 16/25），在EGFR突变阳性肿瘤患者中观察到较高的DCR 66.7%（n = 8/12）。在总体人群中，中位PFS为8.4周，中位OS为50.4周。最常见的阿法替尼相关不良事件是皮疹/痤疮（83%）和腹泻（78%）。结论：一线或二线阿法替尼在EGFR FISH阳性晚期非小细胞肺癌患者中表现出初步活性和可管理的安全性。
Introduction: Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non-small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation.Methods: EGFR gene overexpression was assessed by FISH analysis; patients with high polysomy or gene amplification were considered FISH positive. Patients received daily afatinib less than or equal to 50 mg (monotherapy). Endpoints included objective response rate (ORR; primary), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results: Of 223 patients screened, 69 patients were FISH-positive and met eligibility criteria for treatment. The ORR was 13.0% overall (n = 9 of 69). Higher ORRs were observed in patients with gene amplification (20.0%; n = 5 of 25) and EGFR mutation-positive tumors (25.0%; n = 3 of 12). The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related adverse events were rash/acne (83%) and diarrhea (78%).Conclusions: First-or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non-small-cell lung cancer.