Lee Tai-Huang, Chen Hsiao-Ling, Chang Hsiu-Mei, Wu Chiou-Mei, Wu Kuan-Li, Kuo Chia-Yu, Wei Po-Ju, Chen Chin-Ling, Liu Hui-Lin, Hung Jen-Yu, Yang Chih-Jen, Chong Inn-Wen
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan.
J Clin Med. 2022 Jun 12;11(12):3366. doi: 10.3390/jcm11123366.
Patients with advanced non-small cell lung cancer (NSCLC) who harbor susceptible epidermal growth factor receptor (EGFR) mutations and are treated with EGFR tyrosine kinase inhibitors (TKIs) show longer progression-free survival (PFS) than those treated with chemotherapy. However, developed EGFR-TKI resistance limits PFS improvements. Currently, combination treatment with EGFR-TKIs and anti-angiogenic agents is considered a beneficial regimen for advanced-stage NSCLC harboring susceptible EGFR mutations. However, several trials reported osimertinib plus bevacizumab failed to show superior efficacy over osimertinib alone. However, subgroup analysis showed significantly longer PFS among patients with a history of smoking over those who never smoked. We performed a comprehensive systematic review and meta-analysis to evaluate the smoking status impact. At the end of the process, a total of 2068 patients from 11 randomized controlled trials (RCTs) were included in our meta-analysis. Overall, combination EGFR-TKI plus anti-angiogenic agent treatment showed significantly better PFS among patients with a smoking history (Hazard Ratio (HR) = 0.59, 95% confidence interval (CI) = 0.48-0.73). Erlotinib-based combination therapy showed positive PFS benefits regardless of smoking status (HR = 0.54, 95%CI = 0.41-0.71 for ever smoker, HR = 0.69, 95%CI = 0.54-0.87 for never smoker). Combination therapy prolonged PFS significantly regardless of ethnicity (HR: 0.64, 95% CI: 0.44-0.93 for Asian RCTs, HR: 0.55, 95% CI: 0.41-0.74 for global and non-Asian RCTs). PROSPERO registration number is CRD42022304198).
携带敏感表皮生长因子受体（EGFR）突变并接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的晚期非小细胞肺癌（NSCLC）患者，其无进展生存期（PFS）比接受化疗的患者更长。然而，EGFR-TKI耐药的出现限制了PFS的改善。目前，EGFR-TKIs与抗血管生成药物联合治疗被认为是治疗携带敏感EGFR突变的晚期NSCLC的有益方案。然而，多项试验报告称，奥希替尼联合贝伐单抗并未显示出比单独使用奥希替尼更优的疗效。然而，亚组分析显示，有吸烟史的患者的PFS明显长于从不吸烟的患者。我们进行了一项全面的系统评价和荟萃分析，以评估吸烟状态的影响。在该过程结束时，我们的荟萃分析纳入了来自11项随机对照试验（RCT）的2068例患者。总体而言，EGFR-TKI联合抗血管生成药物治疗在有吸烟史的患者中显示出显著更好的PFS（风险比（HR）=0.59，95%置信区间（CI）=0.48-0.73）。基于厄洛替尼的联合治疗无论吸烟状态如何均显示出积极的PFS获益（曾经吸烟者的HR=0.54，95%CI=0.41-0.71；从不吸烟者的HR=0.69，95%CI=0.54-0.87）。联合治疗无论种族如何均显著延长了PFS（亚洲RCT的HR：0.64，95%CI：0.44-0.93；全球和非亚洲RCT的HR：0.55，95%CI：0.41-0.74）。PROSPERO注册号为CRD42022304198。
