Li Yong Xing, Yang Jian Ye, Xu Yu Fen, Zhang Ming, Zhang Xiao Ping, Chen Wen Yu, Lv Xiao Dong
Department of Respiration, Shaoxing Municipal Hospital, Affiliated Hospital of Shaoxing University, Shaoxing 312000, Zhejiang, China.
Department of Oncology, The First Hospital of Jiaxing, First Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China.
Math Biosci Eng. 2019 Jun 19;16(5):5687-5696. doi: 10.3934/mbe.2019283.
: The current standard approach to the treatment of patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitizing mutations has been the treatment with a first-generation EGFR-TKIs. While, with resistance developed against first-generation EGFR-TKIs, second/third-generation TKIs have attracted all the attention, and replaced first-generation EGFR- TKIs upon disease progression due to the greater efficacy and more favorable tolerability. In the past few years, this strategy has been challenged by clinical evidence when next-generation EGFR-TKIs are used in patients with advanced NSCLC. In this study, we performed a meta- analysis to investigate the efficacy of next-generation TKIs comparison with first-generation TKIs in the treatment of NSCLC. The multiple databases including Pubmed, Embase, Cochrane library databases were adopted to search for the relevant studies, and full-text articles involving to comparison of next-generation TKIs and first-generation TKIs were reviewed. After rigorous reviewing on quality, the data was extracted from eligible randomized controlled trial (RCT). Meta-analysis Revman 5.3 software was used to analyze the combined pooled ORs with the corresponding 95% confidence interval using fixed- or random-effects models according to the heterogeneity. Results: A total of 5 randomized controlled trials were included in this analysis. The group of next-generation TKIs did achieved benefit in progression-free survival (PFS) (OR = 0.58, 95%CI = 0.45-0.75, P＜0.0001), overall survival (OS) (OR = 0.76, 95%CI = 0.65-0.90, P = 0.001) as well with the objective response rate (ORR) (OR = 1.27, 95%CI = 1.01-1.61, P = 0.04), respectively. In the results of subgroup analysis of PFS with EGFR mutations, there is also significant differences with exon 19 deletion (OR = 0.56, 95%CI = 0.41-0.77, P = 0.0003) and exon 21 (L858R) mutation (OR = 0.60, 95%CI = 0.49-0.75, P＜＝0.00001). While, the treatment-related severe adverse event (SAE) between the next-generation TKIs and first-generation TKIs did not have statistical significance (OR = 1.48, 95%CI = 0.62-3.55, P = 0.38). Conclusion: The next-generation TKIs significantly improved efficacy outcomes in the treatment of EGFR mutation-positive advanced NSCLC compared with the first-generation TKIs, with a manageable safety profile. These results are potentially important for clinical decision making for these patients.
目前，对于携带表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）敏感突变的非小细胞肺癌（NSCLC）患者，标准治疗方法是使用第一代EGFR-TKI进行治疗。然而，随着对第一代EGFR-TKI产生耐药性，第二代/第三代TKI引起了广泛关注，并在疾病进展时因其更高的疗效和更好的耐受性而取代了第一代EGFR-TKI。在过去几年中，当在晚期NSCLC患者中使用下一代EGFR-TKI时，这一策略受到了临床证据的挑战。在本研究中，我们进行了一项荟萃分析，以研究下一代TKI与第一代TKI在治疗NSCLC方面的疗效。采用包括Pubmed、Embase、Cochrane图书馆数据库在内的多个数据库搜索相关研究，并对涉及下一代TKI与第一代TKI比较的全文文章进行了综述。在对质量进行严格审查后，从符合条件的随机对照试验（RCT）中提取数据。使用Meta分析Revman 5.3软件，根据异质性，使用固定效应或随机效应模型分析合并后的汇总OR值及其相应的95%置信区间。结果：本分析共纳入5项随机对照试验。下一代TKI组在无进展生存期（PFS）（OR = 0.58，95%CI = 0.45 - 0.75，P＜0.0001）、总生存期（OS）（OR = 0.76，95%CI = 0.65 - 0.90，P = 0.001）以及客观缓解率（ORR）（OR = 1.27，95%CI = 1.01 - 1.61，P = 0.04）方面均取得了益处。在EGFR突变的PFS亚组分析结果中，外显子19缺失（OR = 0.56，95%CI = 0.41 - 0.77，P = 0.0003）和外显子21（L858R）突变（OR = 0.60，95%CI = 0.49 - 0.75，P＜＝0.00001）也存在显著差异。然而，下一代TKI与第一代TKI之间的治疗相关严重不良事件（SAE）没有统计学意义（OR = 1.48，95%CI = 0.62 - 3.55，P = 0.38）。结论：与第一代TKI相比，下一代TKI在治疗EGFR突变阳性的晚期NSCLC方面显著提高了疗效，且安全性可控。这些结果对这些患者的临床决策可能具有重要意义。
