Data from: Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis

Objectives: Bevacizumab and erlotinib inhibit different tumour growth pathways, and both exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC.

Methods: Randomised controlled trials (RCTs) published in PubMed, Web of Science and EMBASE were systematically reviewed. The main outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events. Results were expressed as HRs or risk ratios (RRs) with 95% CIs.

Results: 5 RCTs involving a total of 1736 patients were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19 to 3.06; p=0.007) in the second-line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95% CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI 0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI 0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhoea was higher in the combination group than in the monotherapy group.

Conclusions: The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea. Further well-conducted, large-scale trials are needed to validate these findings.

研究目的：贝伐珠单抗（Bevacizumab）与厄洛替尼（erlotinib）可分别抑制不同的肿瘤生长通路，二者在非小细胞肺癌（non-small-cell lung cancer, NSCLC）的治疗中均展现出临床获益。然而，贝伐珠单抗联合厄洛替尼的治疗疗效仍存在争议。为此，本研究开展一项荟萃分析，对比贝伐珠单抗联合厄洛替尼与单药治疗非小细胞肺癌的效果。

研究方法：系统检索PubMed、Web of Science及EMBASE数据库中已发表的随机对照试验（randomised controlled trials, RCTs）。主要结局指标包括总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、客观缓解率（overall response rate, ORR）及不良事件。研究结果以风险比（HR）或相对危险度（RR）结合95%置信区间（CI）表示。

研究结果：本荟萃分析共纳入5项随机对照试验，涉及1736例患者。与贝伐珠单抗或厄洛替尼单药治疗相比，贝伐珠单抗联合厄洛替尼可显著改善非小细胞肺癌二线治疗的无进展生存期（HR=0.63, 95%CI 0.53~0.75; p=0.000）与客观缓解率（RR=1.91, 95%CI 1.19~3.06; p=0.007）。但两组总生存期无显著差异（HR=0.96, 95%CI 0.83~1.11; p=0.573）。亚组分析显示，年龄<65岁（HR=0.74, 95%CI 0.57~0.96; p=0.026）、亚洲/太平洋岛民种族（HR=0.23, 95%CI 0.10~0.54; p=0.001）、东部肿瘤协作组体能状态评分（Eastern Cooperative Oncology Group performance status, ECOG PS）1分（HR=0.82, 95%CI 0.68~0.98; p=0.033）、ⅢB期或Ⅳ期疾病（HR=0.68, 95%CI 0.57~0.82; p=0.000）以及无吸烟史（HR=0.48, 95%CI 0.32~0.71; p=0.000）的患者可从联合治疗中获得最大的无进展生存期获益。联合治疗组3/4级不良事件（如皮疹、腹泻）的发生率高于单药治疗组。

研究结论：在非小细胞肺癌的二线治疗中，在厄洛替尼基础上加用贝伐珠单抗可显著改善无进展生存期与客观缓解率，且皮疹、腹泻等不良事件风险可控且可接受。未来仍需开展大规模、设计严谨的临床试验以验证本研究结果。