Burotto Mauricio, Manasanch Elisabet E, Wilkerson Julia, Fojo Tito
Medical Oncology and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Medical Oncology and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncologist. 2015 Apr;20(4):400-10. doi: 10.1634/theoncologist.2014-0154. Epub 2015 Mar 20.
Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been evaluated in patients with metastatic and advanced non-small cell lung cancer (NSCLC). The U.S. Food and Drug Administration initially granted accelerated approval to gefitinib but subsequently rescinded the authorization. Erlotinib and afatinib are similar compounds approved for the treatment of metastatic NSCLC. The objective of this study was to compare the efficacy and toxicity of erlotinib, gefitinib, and afatinib in NSCLC.
We tabulated efficacy variables including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) and quantitated toxicities and rates of dose reductions and discontinuation. Summary odds ratios were calculated using random and fixed-effects models. An odds ratio was the summary measure used for pooling of studies.
We examined 28 studies including three randomized trials with afatinib. Clinical toxicities, including pruritus, rash, anorexia, diarrhea, nausea, fatigue, mucositis, paronychia, and anemia, were similar between erlotinib and gefitinib, although some statistical differences were observed. Afatinib treatment resulted in more diarrhea, rash, and paronychia compared with erlotinib and gefitinib. Regarding efficacy, similar outcomes were recorded for ORR, PFS, or OS in the total population and in specific subgroups of patients between erlotinib and gefitinib. All three TKIs demonstrated higher ORRs in first line in tumors harboring EGFR mutations.
Gefitinib has similar activity and toxicity compared with erlotinib and offers a valuable alternative to patients with NSCLC. Afatinib has similar efficacy compared with erlotinib and gefitinib in first-line treatment of tumors harboring EGFR mutations but may be associated with more toxicity, although further studies are needed. Gefitinib deserves consideration for U.S. marketing as a primary treatment for EGFR-mutant NSCLC.
针对表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂（TKIs）已在转移性和晚期非小细胞肺癌（NSCLC）患者中进行了评估。美国食品药品监督管理局最初批准吉非替尼加速上市，但随后撤销了该授权。厄洛替尼和阿法替尼是被批准用于治疗转移性NSCLC的类似化合物。本研究的目的是比较厄洛替尼、吉非替尼和阿法替尼在NSCLC中的疗效和毒性。
我们将疗效变量制成表格，包括总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS），并对毒性、剂量减少率和停药率进行量化。使用随机和固定效应模型计算汇总比值比。比值比是用于汇总研究的汇总指标。
我们审查了28项研究，其中包括三项阿法替尼的随机试验。厄洛替尼和吉非替尼的临床毒性相似，包括瘙痒、皮疹、厌食、腹泻、恶心、疲劳、黏膜炎、甲沟炎和贫血，尽管观察到了一些统计学差异。与厄洛替尼和吉非替尼相比，阿法替尼治疗导致更多的腹泻、皮疹和甲沟炎。在疗效方面，厄洛替尼和吉非替尼在总人群和特定亚组患者中的ORR、PFS或OS记录相似。所有三种TKIs在一线治疗EGFR突变肿瘤时均显示出较高的ORR。
与厄洛替尼相比，吉非替尼具有相似的活性和毒性，为NSCLC患者提供了有价值的替代方案。在一线治疗EGFR突变肿瘤时，阿法替尼与厄洛替尼和吉非替尼的疗效相似，但可能毒性更大，尽管还需要进一步研究。吉非替尼值得考虑在美国作为EGFR突变NSCLC的主要治疗药物上市。
