Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Department of Oncology, Jining No. 1 People's Hospital, Jining, China.
Front Immunol. 2022 Jun 21;13:909027. doi: 10.3389/fimmu.2022.909027. eCollection 2022.
Atezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.
Randomized clinical trials (RCTs) in the Cochrane Library, PubMed, Embase Science Direct, and Google Scholar, together with major oncology conferences that compared atezolizumab with chemotherapy-based treatment for individuals with advanced NSCLC published prior to February 2022, were searched. Studies, bias risk assessment, and data extraction were selected by two independent authors. We extracted the basic features of the included studies, together with the 95% confidence interval (CI) and hazard ratios (HRs), from all patients and subgroups. The combined treatment data were assessed using the inverse variance weighting method.
Seven RCTs including 4,859 patients were included. Our meta-analysis findings indicated that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77-0.88; < 0.00001) and PFS (HR 0.72; 95% CI, 0.61-0.85; < 0.0001) in patients with advanced NSCLC compared with chemotherapy-based treatment. Atezolizumab substantially enhanced OS in patients aged <65 years old and 65-74 years old, those with wild-type EGFR, those without liver metastases, active or previous smokers, white patients and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, and TC0 and IC0, but not in patients aged ≥75 years, never smokers, those with liver metastases, those with EGFR mutant, Asians, Black or African Americans, or those with TC1/2 or IC1/2. Patients with advanced NSCLC who received atezolizumab showed OS improvement regardless of sex (male or female), histological type (non-squamous or squamous NSCLC), performance status (0 or 1), and line of treatment (1st-line therapy or ≥2nd-line therapy). Subgroup analysis revealed that male individuals, those with non-squamous NSCLC, those with PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 achieved OS benefit from atezolizumab treatment not related to the treatment line and treatment regimen.
Age group, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression can be used to predict the potency of atezolizumab and provide a better treatment regimen for patients with advanced NSCLC to achieve accurate and personalized treatment.
阿替利珠单抗已成为治疗非小细胞肺癌(NSCLC)的重要疗法,但仍需进一步提高其疗效。本研究旨在明确阿替利珠单抗在具有不同临床和分子特征的晚期 NSCLC 患者中的疗效,并选择更好的阿替利珠单抗治疗方案,以在免疫治疗中实现更精准的治疗。
检索了 Cochrane 图书馆、PubMed、Embase Science Direct 和 Google Scholar 中的随机对照试验(RCT),以及截至 2022 年 2 月之前在主要肿瘤学会议上发表的比较阿替利珠单抗与基于化疗治疗晚期 NSCLC 患者的研究。由两位独立作者进行研究选择、偏倚风险评估和数据提取。我们从所有患者和亚组中提取了纳入研究的基本特征,以及 95%置信区间(CI)和风险比(HR)。采用方差倒数加权法评估联合治疗数据。
共纳入 7 项 RCT,包括 4859 例患者。我们的荟萃分析结果表明,与基于化疗的治疗相比,阿替利珠单抗显著延长了晚期 NSCLC 患者的总生存期(HR 0.82;95%CI,0.77-0.88;<0.00001)和无进展生存期(HR 0.72;95%CI,0.61-0.85;<0.0001)。在年龄<65 岁和 65-74 岁、EGFR 野生型、无肝转移、活跃或既往吸烟者、白种人以及 TC3 或 IC3、TC2/3 或 IC2/3、TC1/2/3 或 IC1/2/3、TC0 和 IC0 的患者中,阿替利珠单抗显著延长了总生存期,但在年龄≥75 岁、从不吸烟者、肝转移、EGFR 突变、亚洲人、黑人和非裔美国人或 TC1/2 或 IC1/2 的患者中未观察到这种作用。接受阿替利珠单抗治疗的晚期 NSCLC 患者,无论性别(男性或女性)、组织学类型(非鳞状或鳞状 NSCLC)、体能状态(0 或 1)和治疗线数(一线治疗或≥二线治疗),均能改善总生存期。亚组分析显示,男性、非鳞状 NSCLC、PS 1、活跃或既往吸烟者、EGFR 野生型、TC3 或 IC3 以及 TC1/2/3 或 IC1/2/3 的患者,无论治疗线数和治疗方案如何,均能从阿替利珠单抗治疗中获得生存获益。
年龄组、吸烟史、肝转移状态、EGFR 突变状态、种族和 PD-L1 表达可用于预测阿替利珠单抗的疗效,并为晚期 NSCLC 患者提供更好的治疗方案,以实现准确的个体化治疗。