Division of Medical Oncology, SG Moscati Hospital, Avellino, Italy.
Lung Cancer. 2011 Apr;72(1):3-8. doi: 10.1016/j.lungcan.2010.12.009. Epub 2011 Jan 8.
Randomized trials comparing gefitinib with chemotherapy as first-line treatment in patients with EGFR mutated advanced NSCLC support gefitinib as a new, highly effective treatment option in this setting. However, its use in clinical practice has several relevant implications and open issues. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures. Every effort should be made in order to obtain sufficient tissue. If a clinical enrichment has to be performed for selecting patients to test for EGFR mutation, a reasonable proposal is to test all non-squamous tumors, and patients with squamous tumors only if never smokers. In patients with EGFR mutated tumor, one major issue is the decision about immediate use of gefitinib as first-line, or after failure of standard chemotherapy. First-line gefitinib, compared to chemotherapy, is associated with longer progression-free survival, higher response rate, better toxicity profile and quality of life, and its administration as first-line warrants that all patients have the chance of receiving an EGFR inhibitor. Evidence about the efficacy of erlotinib in the same setting will be soon available, however, at the moment, there are no direct comparisons between gefitinib and erlotinib in EGFR mutated patients. Treatment with gefitinib is usually well tolerated. Typical side effects in most cases are of mild to moderate intensity, and usually manageable with temporary interruption of treatment. When indicated gefitinib appears feasible also in special populations, like elderly or unfit patients, characterized by a significantly poorer risk/benefit ratio with standard chemotherapy. Personalized medicine for patients with lung cancer is now a reality, and patients with EGFR mutation should be treated with first-line EGFR tyrosine kinase inhibitor.
随机对照临床试验比较吉非替尼与化疗作为 EGFR 突变晚期 NSCLC 的一线治疗，支持吉非替尼作为该治疗环境中的一种新的、高效的治疗选择。然而，其在临床实践中的应用有几个相关的影响和未解决的问题。为了选择最佳治疗方案，现在需要进行分子特征分析，作为基线诊断程序的一部分。应尽一切努力获取足够的组织。如果需要进行临床富集以选择进行 EGFR 突变检测的患者，一个合理的建议是检测所有非鳞状肿瘤，而对于从不吸烟的鳞状肿瘤患者仅进行检测。在 EGFR 突变肿瘤患者中，一个主要问题是决定立即使用吉非替尼作为一线治疗，还是在标准化疗失败后使用。与化疗相比，一线使用吉非替尼与更长的无进展生存期、更高的缓解率、更好的毒性特征和生活质量相关，并且一线使用吉非替尼保证所有患者都有机会接受 EGFR 抑制剂治疗。关于厄洛替尼在相同环境中的疗效的证据将很快获得，然而，目前在 EGFR 突变患者中，吉非替尼和厄洛替尼之间没有直接比较。吉非替尼治疗通常耐受性良好。大多数情况下，典型的副作用为轻至中度，通常可以通过暂时中断治疗来管理。在有指征的情况下，吉非替尼也适用于特殊人群，如老年或身体不适的患者，他们接受标准化疗的风险/获益比明显较差。肺癌的个体化治疗现在已经成为现实，具有 EGFR 突变的患者应接受一线 EGFR 酪氨酸激酶抑制剂治疗。
