Sanford Mark, Scott Lesley J
Adis, North Shore, Auckland, New Zealand.
Drugs. 2009 Nov 12;69(16):2303-28. doi: 10.2165/10489100-000000000-00000.
Gefitinib (Iressa) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), in particular in those who are harbouring EGFR mutations. In a large phase III trial (IPASS) in chemotherapy-naive Asian patients with adenocarcinoma who were never smokers or former light smokers, oral gefitinib was more effective than carboplatin plus paclitaxel in prolonging progression-free survival (PFS). In a prespecified subgroup analysis, EGFR-mutation-positive status was associated with a positive response to gefitinib treatment. Furthermore, a trial in chemotherapy-naive patients with NSCLC that was restricted to those with EGFR mutations found that gefitinib recipients had significantly longer PFS than carboplatin plus paclitaxel recipients. In large phase III trials (INTEREST, V-15-32) in unselected, previously treated patients, the overall survival (OS) in gefitinib recipients was noninferior to, or not significantly different from, that of docetaxel recipients. In a placebo-controlled trial in previously treated patients (ISEL), pre-planned subgroup analyses in Asian patients and non-smokers showed that in these subgroups gefitinib prolonged OS, and that EGFR biomarkers predicted a positive response to gefitinib. Gefitinib was also associated with greater improvements in quality of life (QOL) in both chemotherapy-naive and previously treated patients. A head-to-head trial of gefitinib versus erlotinib in EGFR-mutation-positive patients would help position gefitinib relative to erlotinib in this population. Further research is also required to identify factors associated with non-response to EGFR-tyrosine-kinase inhibitors in EGFR-mutation-positive patients. Gefitinib was a generally well tolerated treatment, with rash and diarrhoea being the most common treatment-emergent adverse events. Interstitial lung disease (ILD) is a serious co-morbidity of NSCLC associated with gefitinib and other cancer treatments; ILD-type events occurred with an overall incidence of approximately 1% in gefitinib recipients participating in clinical trials, and were more common in Asian patients. Notably, gefitinib was associated with significantly fewer haematological and neurological adverse effects than comparator chemotherapy regimens. Gefitinib as monotherapy is an effective treatment for patients with locally advanced or metastatic NSCLC with EGFR mutations.
吉非替尼（易瑞沙）是一种表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，用于治疗局部晚期或转移性非小细胞肺癌（NSCLC）患者，特别是那些携带EGFR突变的患者。在一项针对未接受过化疗、从不吸烟或曾经轻度吸烟的亚洲腺癌患者的大型III期试验（IPASS）中，口服吉非替尼在延长无进展生存期（PFS）方面比卡铂加紫杉醇更有效。在一项预先设定的亚组分析中，EGFR突变阳性状态与对吉非替尼治疗的阳性反应相关。此外，一项仅限于EGFR突变患者的未接受过化疗的NSCLC患者试验发现，接受吉非替尼治疗的患者的PFS明显长于接受卡铂加紫杉醇治疗的患者。在针对未选择的、先前接受过治疗的患者的大型III期试验（INTEREST、V-15-32）中，接受吉非替尼治疗的患者的总生存期（OS）不劣于多西他赛治疗的患者，或与多西他赛治疗的患者无显著差异。在一项针对先前接受过治疗的患者的安慰剂对照试验（ISEL）中，对亚洲患者和非吸烟者进行的预先计划的亚组分析表明，在这些亚组中吉非替尼延长了OS，并且EGFR生物标志物预测了对吉非替尼的阳性反应。吉非替尼还与未接受过化疗和先前接受过治疗的患者的生活质量（QOL）的更大改善相关。在EGFR突变阳性患者中进行吉非替尼与厄洛替尼的头对头试验将有助于确定吉非替尼相对于厄洛替尼在该人群中的地位。还需要进一步研究以确定与EGFR突变阳性患者对EGFR酪氨酸激酶抑制剂无反应相关的因素。吉非替尼是一种耐受性普遍良好的治疗方法，皮疹和腹泻是最常见的治疗中出现的不良事件。间质性肺病（ILD）是与吉非替尼和其他癌症治疗相关的NSCLC的一种严重合并症；在参与临床试验的接受吉非替尼治疗的患者中，ILD类型事件的总体发生率约为1%，在亚洲患者中更常见。值得注意的是，与对照化疗方案相比，吉非替尼引起的血液学和神经学不良反应明显较少。吉非替尼单药治疗是治疗具有EGFR突变的局部晚期或转移性NSCLC患者的一种有效治疗方法。
