Zhang Lei, Ren Hong-Wei, Wu Qi-Long, Wu Yan-Juan, Song Xiang
Department of Oncology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Xinghualing District, Taiyuan, 030013, Shanxi, China.
Department of Cardio-Thoracic Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Pathol Oncol Res. 2020 Apr;26(2):1137-1143. doi: 10.1007/s12253-019-00669-2. Epub 2019 May 31.
Resistance develops against first-generation tyrosine kinase inhibitors (TKIs), which target the epidermal growth factor receptor (EGFR), after a while for non-small-cell lung cancer (NSCLC). Recently, researchers have developed specific inhibitors against them. Among those inhibitors, next-generation EGFR-TKIs have gained prominence due to the greater efficacy and more favorable tolerability. Today, the efficacy of next-generation EGFR-TKIs in patients with advanced NSCLC after failure on first-generation EGFR-TKIs still remains under investigation. The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation EGFR-TKIs in advanced NSCLC after failure on first-generation EGFR-TKIs. We performed a comprehensive search of the several electronic databases to September, 2018 to identify clinical trials. The primary endpoint was overall survival (OS), progression-free survival (PFS), disease controlled rate (DCR), objective response rate (ORR), and adverse events (AEs). Severe adverse events (AEs) (grade ≥ 3) based on the EGFR-TKIs were analysed. Odds Ratio (OR) along with 95% confidence interval (95% CI) were utilized for the main outcome analysis. In total, we had 3 randomized controlled trials in this analysis. The group of next-generation EGFR-TKIs was significantly improved PFS (OR = 0.34,95%CI = 0.29-0.40, P < 0.00001), as well with the ORR (OR = 10.48,95%CI = 3.87-28.34, P < 0.00001) and DCR (OR = 6.03,95%CI = 4.41-8.25, P < 0.00001), respectively. However, there is no significant difference in overall survival with next-generation EGFR-TKIs (OR = 1.05,95%CI = 0.85-1.31, P = 0.66). While, the OR for the treatment-related AEs of grade 3 or 4 (diarrhoea, rash/acne, nausea, vomiting, anemia) between the patients who received next-generation EGFR-TKIs and chemotherapy did not show safety benefit (P>0.05). Next-generation EGFR-TKIs was shown to be the better agent to achieve higher response rate and the longer PFS in NSCLC patients as the later-line therapy for previously treated patients with first-generation EGFR-TKIs. While, the benefit of the OS and safety compared with the chemotherapy did not achieved. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.
对于非小细胞肺癌（NSCLC）患者，一段时间后会对第一代靶向表皮生长因子受体（EGFR）的酪氨酸激酶抑制剂（TKIs）产生耐药性。最近，研究人员已开发出针对它们的特异性抑制剂。在这些抑制剂中，第二代EGFR-TKIs因其更高的疗效和更好的耐受性而备受关注。目前，第二代EGFR-TKIs在第一代EGFR-TKIs治疗失败后的晚期NSCLC患者中的疗效仍在研究中。本荟萃分析的目的是系统评估第二代EGFR-TKIs在第一代EGFR-TKIs治疗失败后的晚期NSCLC患者中的疗效和安全性。我们全面检索了多个电子数据库至2018年9月以识别临床试验。主要终点为总生存期（OS）、无进展生存期（PFS）、疾病控制率（DCR）、客观缓解率（ORR）和不良事件（AE）。分析了基于EGFR-TKIs的严重不良事件（AE）（≥3级）。比值比（OR）及95%置信区间（95%CI）用于主要结局分析。本分析共纳入3项随机对照试验。第二代EGFR-TKIs组的PFS（OR = 0.34，95%CI = 0.29 - 0.40，P < 0.00001）、ORR（OR = 10.48，95%CI = 3.87 - 28.34，P < 0.00001）和DCR（OR = 6.03，95%CI = 4.41 - 8.25，P < 0.00001）均显著改善。然而，第二代EGFR-TKIs在总生存期方面无显著差异（OR = 1.05，95%CI = 0.85 - 1.31，P = 0.66）。同时，接受第二代EGFR-TKIs治疗的患者与接受化疗的患者相比，3或4级治疗相关AE（腹泻、皮疹/痤疮、恶心、呕吐、贫血）的OR未显示出安全性优势（P>0.05）。第二代EGFR-TKIs被证明是作为第一代EGFR-TKIs治疗过的患者的二线治疗，在NSCLC患者中实现更高缓解率和更长PFS的更好药物。然而，与化疗相比，在OS和安全性方面未显示出优势。需要进一步研究以建立所有EGFR突变及其对不同治疗的个体影响的数据库。
