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

BackgroundThe 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.MethodsUsing 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.ResultsThe 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.ConclusionsThe 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 registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692

DataSheet_1_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.docx

BackgroundThe 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.MethodsUsing 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.ResultsThe bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54–0.73, p ConclusionsThe 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 registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.</p

A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period.

AIM:We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. MATERIAL AND METHODS:In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. RESULTS:In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). CONCLUSION:The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance