Tsukita Yoko, Inoue Akira
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, Japan.
Jpn J Clin Oncol. 2022 Apr 22. doi: 10.1093/jjco/hyac012.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been established as the standard first-line treatment for patients with previously untreated advanced non-small cell lung cancer (NSCLC) with an EGFR activating mutation. In the FLAURA study, osimertinib, third-generation EGFR-TKI, resulted in significantly longer progression-free survival and overall survival (OS) than first-generation EGFR-TKIs (gefitinib or erlotinib) in patients with previously untreated advanced NSCLC with an EGFR activating mutation. Osimertinib is now widely used as first-line therapy for those patients. In Japanese subset analysis of the FLAURA study, the median progression-free survival was prolonged by osimertinib (19.1 months) relative to gefitinib (13.8 months). However, there was no apparent OS benefit, albeit at the level of an exploratory post-hoc analysis. Although the safety profile in the Japanese subset was generally consistent with the overall population, the incidence of liver enzyme increases in the gefitinib group and that of interstitial lung disease/pneumonitis in the osimertinib group was higher among Japanese patients. There is now an increasing number of first-line treatment options for NSCLC with EGFR mutations, including EGFR-TKIs in combination with platinum-doublet chemotherapy or anti-angiogenic drugs. These combinations show progression-free survival benefits similar to osimertinib regardless of the mutation type. Therefore, a first-line combination regimen followed by osimertinib remains an attractive strategy. We review data from the randomized clinical trials of first-line EGFR-TKIs including a subset of Japanese patients and discuss first-line therapies for patients with NSCLC harbouring EGFR mutations.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）已被确立为先前未接受过治疗的晚期非小细胞肺癌（NSCLC）且具有EGFR激活突变患者的标准一线治疗方案。在FLAURA研究中，第三代EGFR-TKI奥希替尼在先前未接受过治疗的晚期NSCLC且具有EGFR激活突变的患者中，与第一代EGFR-TKIs（吉非替尼或厄洛替尼）相比，显著延长了无进展生存期和总生存期（OS）。奥希替尼现被广泛用作这些患者的一线治疗。在FLAURA研究的日本亚组分析中，奥希替尼（19.1个月）相对于吉非替尼（13.8个月）延长了中位无进展生存期。然而，尽管处于探索性事后分析水平，但未观察到明显的总生存期获益。虽然日本亚组的安全性概况总体上与总体人群一致，但吉非替尼组肝酶升高的发生率以及奥希替尼组间质性肺病/肺炎的发生率在日本患者中更高。目前，对于具有EGFR突变的NSCLC有越来越多的一线治疗选择，包括EGFR-TKIs联合铂类双联化疗或抗血管生成药物。无论突变类型如何，这些联合方案均显示出与奥希替尼相似的无进展生存期获益。因此，一线联合方案序贯奥希替尼仍然是一个有吸引力的策略。我们回顾了包括日本患者亚组在内的一线EGFR-TKIs随机临床试验的数据，并讨论了具有EGFR突变的NSCLC患者的一线治疗方法。
