*Istituto Toscano Tumori, Ospedale Civile di Livorno, Livorno, Italy; †Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS, Rozzano, Italy; ‡IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro, Lung Cancer Unit, Genova, Italy; §San Gerardo Hospital, Monza, Italy; ‖Istituto Oncologico Veneto IRCSS, Padova, Italy; ¶Clinical Research Center, Center of Excellence on Aging, University Foundation, Chieti, Italy; #IRCCS Humanitas Clinical Institute, Rozzano, Milan, Italy; **Boehringer Ingelheim Pharma GmbH & Co. KG, Vienna, Austria; ††Boehringer Ingelheim Italia SpA, Milan, Italy; and ‡‡Boehringer Ingelheim Ltd., Bracknell, UK.
J Thorac Oncol. 2015 Apr;10(4):665-72. doi: 10.1097/JTO.0000000000000442.
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.
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.
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%).
First- or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non-small-cell lung cancer.
阿法替尼是一种口服不可逆的 ErbB 家族阻滞剂，在表皮生长因子受体（EGFR）突变阳性的晚期肺腺癌中显示出疗效和安全性。尚不清楚这种活性是否也发生在 EGFR 基因过表达的患者中，而不论突变状态如何。这项 II 期研究调查了阿法替尼在通过荧光原位杂交（FISH）检测到 EGFR 基因拷贝数增加和/或基因扩增的晚期非小细胞肺癌患者中的活性和安全性，无论 EGFR 突变状态如何。
通过 FISH 分析评估 EGFR 基因过表达；高多倍体或基因扩增的患者被认为是 FISH 阳性。患者接受每日不超过 50mg 的阿法替尼（单药治疗）。主要终点包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和安全性。
在筛选的 223 名患者中，有 69 名 FISH 阳性且符合治疗条件。总体 ORR 为 13.0%（9/69）。在基因扩增（20.0%；25 例中有 5 例）和 EGFR 突变阳性肿瘤（25.0%；12 例中有 3 例）患者中观察到更高的 ORR。总体 DCR 为 50.7%（69 例中有 35 例；中位持续时间：24.9 周），在基因扩增患者中 DCR 更高（64.0%；25 例中有 16 例），在 EGFR 突变阳性肿瘤患者中 DCR 更高（66.7%；12 例中有 8 例）。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反应是皮疹/痤疮（83%）和腹泻（78%）。
一线或二线阿法替尼在 EGFR FISH 阳性的晚期非小细胞肺癌患者中表现出初步疗效和可管理的安全性。
