Effectiveness and safety of the bevacizumab and erlotinib combination versus erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis.

Autor:	Motta-Guerrero R; ALIADA Centro Oncologico, Lima, Peru., Leon Garrido-Lecca A; ALIADA Centro Oncologico, Lima, Peru., Failoc-Rojas VE; ALIADA Centro Oncologico, Lima, Peru.; Universidad Cesar Vallejo, Piura, Peru., Calle-Villavicencio A; ALIADA Centro Oncologico, Lima, Peru., Villacorta-Carranza R; ALIADA Centro Oncologico, Lima, Peru., Huerta-Collado Y; ALIADA Centro Oncologico, Lima, Peru., Torres-Mera A; Universidad Nacional Pedro Ruiz Gallo, Lambayeque, Peru., Valladares-Garrido MJ; Universidad Continental, Lima, Peru., Rivera-Francia V; ALIADA Centro Oncologico, Lima, Peru., Carracedo C; ALIADA Centro Oncologico, Lima, Peru., Raez L; Memorial Healthcare System, Florida, FL, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Jan 23; Vol. 13, pp. 1335373. Date of Electronic Publication: 2024 Jan 23 (Print Publication: 2023).
DOI:	10.3389/fonc.2023.1335373
Abstrakt:	Background: The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC. Methods: Using eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis. Results: The bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54-0.73, p < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64-0.97, p = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78-1.10, p = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76-6.88, p = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs. Conclusions: The bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Motta-Guerrero, Leon Garrido-Lecca, Failoc-Rojas, Calle-Villavicencio, Villacorta-Carranza, Huerta-Collado, Torres-Mera, Valladares-Garrido, Rivera-Francia, Carracedo and Raez.)
Databáze:	MEDLINE
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