Efficacy and safety of osimertinib plus bevacizumab versus osimertinib alone for advanced non–small-cell lung cancer with EGFR mutations: A meta-analysis of randomized controlled trials
Authors: Yao Ling , Zhang Chunzhen , Li Dailong , Xu Lu , Yang Xianfei 
Published: November 2024

Background:
To systematically evaluate the efficacy and safety of osimertinib plus bevacizumab in treating advanced non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Methods:
Up to May 26, 2024, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, Chinese Biomedical Literature, China Science and Technology Journal, and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of osimertinib plus bevacizumab in the treatment of advanced EGFR-mutant NSCLC were included. Two researchers independently screened the literature, assessed the quality of the included literature, and extracted the literature data. Revman5.4 software was used for meta-analysis.

Results:
A total of 824 patients were included in 10 RCTs. The results of meta-analysis showed that compared with the control group (osimertinib alone), the experimental group (osimertinib plus bevacizumab) had a higher objective response rate (ORR) (relative risk [RR] = 1.23, 95% confidence interval [CI] = 1.03–1.47, P = .02), and the experimental group could significantly reduce the expression levels of carcinoembryonic antigen (mean difference [SMD] = 0.82, 95% CI = 0.30–1.35, P = .002), vascular endothelial growth factor (SMD = 0.43, 95% CI = 0.13–0.73, P = .005), neuron-specific enolase (SMD = 0.88, 95% CI = 0.60–1.17, P < .00001), cytokeratin 19 fragments (SMD = 1.33, 95% CI = 0.34–2.33, P = .009), and carbohydrate antigen 125 (SMD = 0.46, 95% CI = 0.15–0.77, P = .004) in serum. However, the experimental group did not significantly improve the disease control rate (DCR) (RR = 1.17, 95% CI = 1.00–1.36, P = .05), 1- and 2-year progression-free survival (PFS) rates (RR = 1.15, 95% CI = 1.00–1.33, P = .05; RR = 1.02, 95% CI = 0.74–1.40, P = .92), 1- and 2-year overall survival (OS) rates (RR = 1.11, 95% CI = 0.92–1.36, P = .28; RR = 0.99, 95% CI = 0.84–1.18, P = .95). Interestingly, the results of subgroup analysis showed that the experimental group significantly improved ORR, DCR, 1-year PFS, and OS rates in the Chinese population and patients under 65 years old (P < .05). In addition, when the dose of bevacizumab was 7.5 mg/kg q3w in the experimental group, ORR, DCR, 1-year PFS, and OS rates were significantly better than those in the control group (P < .05). In terms of adverse events of drugs, the incidence of proteinuria, hypertension, oral mucositis, bleeding, nausea, and vomiting in the experimental group was higher than that in the control group (P < .05).

Conclusion:
For patients with advanced EGFR-mutant NSCLC, osimertinib plus bevacizumab has some clinical benefit compared with osimertinib alone. Still, it does not provide additional long-term survival benefits and has higher toxicity. More well-designed, multicenter RCTs are needed to identify the subgroups of patients most likely to benefit from this combination regimen and to validate the optimal dose of this combination regimen.