Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lung Cancer. 2018 May;119:36-41. doi: 10.1016/j.lungcan.2018.02.020. Epub 2018 Mar 6.
Afatinib, an irreversible ErbB family blocker, approved for first-line treatment of epidermal growth factor receptor (EGFR) mutated advanced non-small cell lung cancer (NSCLC). This study investigated experience of afatinib within a compassionate use program (CUP).
The afatinib CUP was an open-label, multicenter, single-arm program in Korea. We enrolled patients with stage IV NSCLC and who had received at least one line of previous cytotoxic chemotherapy and previous EGFR TKI treatment with either an EGFR mutation or documented clinical benefit. The starting dose of afatinib was 50 mg once daily.
From August 2011 to September 2014, 332 patients received at least one dose of afatinib. Most patients were registered in the CUP for fourth- or fifth-line treatment with afatinib. Adverse events (AEs) occurred in 98.1% of patients, including 29.8% with serious AEs. The most common AEs (all grades) were diarrhea (90.1%) and skin rash (62.0%). Dose reductions occurred in 60.5% of patients and discontinuations due to AEs were reported in 11.1% of patients. The response rate and median time to treatment failure (TTF) were 27.4% and 3.3 months (CI 95%, 2.8-3.8 months), respectively, in this highly pretreated population. In subgroup analysis, ECOG PS 0 or 1 and immediate pretreatment with pemetrexed monotherapy or a platinum doublet were associated with a longer TTF for afatinib.
No additional or unexpected safety concerns were observed, and afatinib demonstrated moderate antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib in a real-world setting.
阿法替尼是一种不可逆的 ErbB 家族阻滞剂，已被批准用于治疗表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）的一线治疗。本研究调查了同情用药计划（CUP）中阿法替尼的应用经验。
阿法替尼 CUP 是韩国的一项开放性、多中心、单臂方案。我们招募了 IV 期 NSCLC 患者，这些患者至少接受过一线细胞毒性化疗，以及之前的 EGFR TKI 治疗，这些治疗有 EGFR 突变或有明确的临床获益。阿法替尼的起始剂量为 50mg，每日一次。
从 2011 年 8 月至 2014 年 9 月，共有 332 名患者接受了至少一剂阿法替尼治疗。大多数患者是在接受第四或第五线阿法替尼治疗时登记参加 CUP 的。98.1%的患者发生了不良反应（AE），包括 29.8%的严重 AE。最常见的 AE（所有等级）是腹泻（90.1%）和皮疹（62.0%）。60.5%的患者需要减少剂量，11.1%的患者因 AE 而停药。在这个高度预处理的人群中，客观缓解率和中位无进展生存期（TTF）分别为 27.4%和 3.3 个月（95%CI，2.8-3.8 个月）。在亚组分析中，ECOG PS 0 或 1 以及立即接受培美曲塞单药或铂类双联化疗预处理与阿法替尼更长的 TTF 相关。
在真实世界环境中，阿法替尼在对吉非替尼或厄洛替尼获得性耐药的晚期 NSCLC 患者中显示出中等的抗肿瘤活性，且未观察到新的或意外的安全性问题。
