Park Keunchil, Wan-Teck Lim Darren, Okamoto Isamu, Yang James Chih-Hsin
Division of Hematology/Oncology, Innovative Cancer Medicine Institute, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, South Korea.
Division of Medical Oncology, National Cancer Center, Singapore.
Ther Adv Med Oncol. 2019 Apr 15;11:1758835919836374. doi: 10.1177/1758835919836374. eCollection 2019.
Afatinib is an ErbB family blocker that is approved for the treatment of epidermal growth factor receptor ( mutation-positive non-small-cell lung cancer (NSCLC). Pivotal randomized clinical studies demonstrated that afatinib significantly prolonged progression-free survival compared with platinum-based chemotherapy (LUX-Lung 3, LUX-Lung 6), and with gefitinib (LUX-Lung 7), with manageable side effects. However, these results were derived from controlled studies conducted in selected patients and are not necessarily representative of real-world use of afatinib. To gain a broader understanding of the effectiveness and safety of first-line afatinib, we have undertaken a literature review of real-world studies that have assessed its use in a variety of patient populations. We focused on patients with uncommon mutations, brain metastases, or those of advanced age, as these patients are often excluded from clinical studies but are regularly seen in routine clinical practice. The available real-world studies suggest that afatinib has clinical activity, and is tolerable, in diverse patient populations in an everyday clinical practice setting. Moreover, consistent with LUX-Lung 7, several real-world comparative studies indicate that afatinib might confer better efficacy than first-generation EGFR tyrosine kinase inhibitors. Tolerability-guided dose adjustment, undertaken in 21-68% of patients in clinical practice, did not appear to reduce the efficacy of afatinib. Taken together, these findings provide further support for the use of afatinib as a treatment option in patients with mutation-positive NSCLC.
阿法替尼是一种表皮生长因子受体(ErbB)家族阻断剂,已被批准用于治疗表皮生长因子受体(EGFR)突变阳性的非小细胞肺癌(NSCLC)。关键的随机临床研究表明,与铂类化疗(LUX-Lung 3、LUX-Lung 6)以及吉非替尼(LUX-Lung 7)相比,阿法替尼显著延长了无进展生存期,且副作用可控。然而,这些结果来自于在特定患者中进行的对照研究,不一定代表阿法替尼在现实世界中的使用情况。为了更全面地了解一线使用阿法替尼的有效性和安全性,我们对评估其在各种患者群体中使用情况的真实世界研究进行了文献综述。我们重点关注了具有罕见突变、脑转移或老年患者,因为这些患者通常被排除在临床研究之外,但在日常临床实践中经常见到。现有的真实世界研究表明,在日常临床实践环境中,阿法替尼在不同患者群体中具有临床活性且耐受性良好。此外,与LUX-Lung 7一致,多项真实世界比较研究表明,阿法替尼可能比第一代EGFR酪氨酸激酶抑制剂具有更好的疗效。在临床实践中,21% - 68%的患者进行了耐受性指导的剂量调整,但这似乎并未降低阿法替尼的疗效。综上所述,这些发现为阿法替尼作为EGFR突变阳性NSCLC患者的治疗选择提供了进一步支持。