LUX-Lung 4 研究：阿法替尼治疗既往接受厄洛替尼、吉非替尼或两者联合治疗后进展的晚期非小细胞肺癌患者的 II 期临床试验。
LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both.
机构信息
Nobuyuki Katakami, Kobe City Medical Center General Hospital, Kobe; Shinji Atagi, National Hospital Organization Kinki-Chuo Chest Medical Center; Koji Takeda, Osaka City General Hospital; Kazuto Nishio, Kinki University, Osaka; Koichi Goto, National Cancer Center Hospital East, Chiba; Toyoaki Hida, Aichi Cancer Center Hospital, Nagoya; Takeshi Horai, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo; Akira Inoue, Tohoku University Hospital, Sendai; Yukito Ichinose, National Kyushu Cancer Center, Fukuoka; Kunihiko Koboyashi, Saitama International Medical Center, Saitama; Katsuyuki Kiura, Okayama University, Okayama; Yoko Seki and Ryuichi Ebisawa, Nippon Boehringer Ingelheim; Nobuyuki Yamamoto, Shizuoka Cancer Center, Shizuoka, Japan; and Mehdi Shahidi, Boehringer Ingelheim, Bracknell, United Kingdom.
出版信息
J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1.
PURPOSE
New molecular targeted agents are needed for patients with non-small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M.
PATIENTS AND METHODS
This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after ≥ 12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatment-related AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease.
CONCLUSION
Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.
目的
对于接受厄洛替尼、吉非替尼或两者联合治疗后进展的非小细胞肺癌（NSCLC）患者，需要新的分子靶向药物。阿法替尼是一种口服的不可逆表皮生长因子受体（EGFR [ErbB1]）家族阻断剂，在具有 EGFR 激活突变的表皮生长因子受体（EGFR）突变模型中具有临床前活性，包括 T790M。
患者和方法
这是一项在先前接受厄洛替尼和/或吉非替尼治疗≥12 周后进展的 IIIB 期至 IV 期肺腺癌日本单臂 II 期试验。患者每天接受阿法替尼 50mg。主要终点为独立评估的客观缓解率（完全缓解或部分缓解）。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。
结果
在 62 例接受治疗的患者中，根据当地和/或中心实验室分析，45 例（72.6%）在原发肿瘤中 EGFR 突变阳性。51 例（82.3%）符合厄洛替尼和/或吉非替尼获得性耐药标准。在 61 例可评估的患者中，5 例（8.2%；95%CI，2.7%至 18.1%）有确认的客观缓解率（部分缓解）。中位 PFS 为 4.4 个月（95%CI，2.8 至 4.6 个月），中位 OS 为 19.0 个月（95%CI，14.9 个月至未达到）。2 例患者发生获得性 T790M 突变：L858R+T790M 和外显子 19 缺失+T790M；他们的疾病稳定分别为 9 个月和 1 个月。最常见的阿法替尼相关不良事件（AE）是腹泻（100%）和皮疹/痤疮（91.9%）。18 例（29%）患者因阿法替尼相关不良事件停止治疗，其中 4 例也出现疾病进展。
结论
在接受厄洛替尼和/或吉非替尼三线或四线治疗后进展且对厄洛替尼、吉非替尼或两者均耐药的 NSCLC 患者中，阿法替尼显示出适度但显著的疗效。
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