Graduate Institute of Oncology and Cancer Research Centre, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lancet Oncol. 2012 May;13(5):539-48. doi: 10.1016/S1470-2045(12)70086-4. Epub 2012 Mar 26.
Afatinib is an irreversible ErbB-family blocker with preclinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. We aimed to assess the efficacy of afatinib in patients with lung adenocarcinoma and EGFR mutations.
In this phase 2 study, we enrolled patients from 30 centres in Taiwan and the USA with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) with EGFR mutations, who had no more than one previous chemotherapy regimen for advanced disease, an Eastern Cooperative Oncology Group performance status of 0-2, and no previous treatment with EGFR tyrosine-kinase inhibitors. We tested two afatinib starting doses: 50 mg daily and subsequently 40 mg daily, introduced to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). This study is registered with ClinicalTrials.gov, number NCT00525148.
129 patients were treated with afatinib, 99 with a starting dose of 50 mg and 30 with a starting dose of 40 mg. 79 (61%) of 129 patients had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 patients with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 patients with less common mutations. Similar proportions of patients had an objective response when analysed by starting dose (18 [60%] of 30 patients at 40 mg vs 61 [62%] of 99 patients at 50 mg). Of the two most common adverse events (diarrhoea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 [22%] of 99 patients for diarrhoea and 28 [28%] of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two [7%] of 30 patients for both diarrhoea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). We recorded one possibly drug-related death (interstitial lung disease).
Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations. The efficacy of afatinib 40 mg should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC.
Boehringer Ingelheim Inc.
阿法替尼是一种不可逆的 ErbB 家族阻滞剂，在具有 EGFR 突变的非小细胞肺癌（NSCLC）的临床前研究中具有活性。我们旨在评估阿法替尼在具有 EGFR 突变的肺腺癌患者中的疗效。
在这项来自台湾和美国的 30 个中心的 2 期研究中，我们招募了患有肺腺癌（有胸腔积液的 IIIb 期或 IV 期）且具有 EGFR 突变的患者，这些患者既往接受过不超过一次晚期疾病的化疗方案，东部合作肿瘤学组的体能状态为 0-2，且未接受过 EGFR 酪氨酸激酶抑制剂的治疗。我们测试了两种阿法替尼的起始剂量：每天 50mg，随后每天 40mg，以确定在保留抗肿瘤活性的情况下能否提高耐受性。主要终点是根据实体瘤反应评估标准 1.0（独立评估）确认的客观缓解（完全缓解或部分缓解）患者的比例。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT00525148。
129 名患者接受了阿法替尼治疗，其中 99 名患者的起始剂量为 50mg，30 名患者的起始剂量为 40mg。129 名患者中有 79 名（61%）有客观缓解（2 名完全缓解，77 名部分缓解）。在具有两种常见激活型 EGFR 突变（缺失 19 或 L858R）的 106 名患者中有 70 名（66%）有客观缓解，23 名具有较少见突变的患者中有 9 名（39%）有客观缓解。当按起始剂量进行分析时，具有相似比例的患者有客观缓解（40mg 组的 30 名患者中有 18 名[60%]，50mg 组的 99 名患者中有 61 名[62%]）。两种最常见的不良反应（腹泻和皮疹或痤疮）中，接受 50mg 起始剂量的患者中 3 级事件更常见（腹泻 99 名患者中有 22 名[22%]，皮疹或痤疮 99 名患者中有 28 名[28%]），而接受 40mg 起始剂量的患者中更常见（腹泻和皮疹或痤疮，30 名患者中有 2 名[7%]）；接受 40mg 起始剂量的患者中可能与治疗相关的严重不良事件也较少（30 名患者中有 2 名，99 名患者中有 14 名）。我们记录了一例可能与药物相关的死亡（间质性肺病）。
阿法替尼在治疗具有 EGFR 突变的晚期肺腺癌患者中显示出活性，特别是在具有缺失 19 或 L858R 突变的患者中。阿法替尼 40mg 的疗效应与化疗或其他 EGFR 酪氨酸激酶抑制剂在 EGFR 突变阳性 NSCLC 中进行比较。
勃林格殷格翰公司。
