Comparative efficacy of immune checkpoint inhibitor–anti-VEGF inhibitor combinations in non–small cell lung carcinoma: A network meta-analysis of randomized trials.
e20629 Background: Concomitant inhibition of the vascular endothelial growth factor (VEGF) pathway together with PD-1 or PD-L1 immune checkpoint blockade has demonstrated synergistic activity in non-small cell lung cancer (NSCLC). However, comparative evidence across individual immune checkpoint inhibitor (ICI) and anti-VEGF combinations remains limited. This network meta-analysis (NMA) aimed to evaluate and compare the efficacy of available ICI plus anti-VEGF combination strategies in NSCLC. Methods: A systematic search of three electronic databases and two clinical trial registries was conducted to identify randomized controlled trials evaluating combinations of ICIs with anti-VEGF agents. A frequentist NMA framework was applied using the netmeta package in R. Hazard ratios (HRs) were used for overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were used for objective response rate (ORR). Treatment ranking was performed using P scores. Results: A total of 24 randomized controlled trials were included in the network. For survival outcomes, the combination of nivolumab plus bevacizumab demonstrated significantly improved OS (HR = 0.66, 95% CI 0.50–0.88) and PFS (HR = 0.46, 95% CI 0.27–0.81) compared with standard chemotherapy. In addition, atezolizumab plus bevacizumab was associated with a significant OS benefit over chemotherapy (HR = 0.79, 95% CI 0.65–0.95). Indirect comparisons showed that nivolumab plus bevacizumab significantly improved PFS compared with pembrolizumab monotherapy, as well as pembrolizumab combined with lenvatinib or chemotherapy. Furthermore, nivolumab combined with sitravatinib demonstrated significantly superior OS and PFS compared with ramucirumab and chemotherapy. For ORR assessed using RECIST 1.1, nivolumab-based combinations could not be incorporated into the network due to insufficient data, and no other combination demonstrated a statistically significant advantage over chemotherapy. However, indirect comparisons showed that pembrolizumab plus lenvatinib was superior to lenvatinib monotherapy (OR = 4.76, 95% CI 1.04–25.0). P-score rankings identified nivolumab plus bevacizumab as the top-ranked regimen for survival outcomes, followed by atezolizumab plus bevacizumab. For ORR, pembrolizumab plus lenvatinib ranked highest, followed by atezolizumab plus bevacizumab. Conclusions: Nivolumab-based ICI and anti-VEGF combinations, particularly with bevacizumab and sitravatinib, demonstrate the most favorable survival outcomes in NSCLC. Evidence for ORR remains limited, and further randomized comparisons are required to better define the relative efficacy of these combinations.
Uncovering prostate cancer and sepsis-related mortality shifts in the USA (1999-2020).
e17104 Background: Prostate cancer is a commonly diagnosed malignancy among men. Sepsis continues to pose a significant threat to outcomes. Patients with are particularly vulnerable to sepsis due to immunosuppression from the malignancy itself, advanced age, and treatment-related factors including catheter use. Sepsis is associated with high short-term mortality, and worsened overall outcomes, underscoring the need for epidemiological and clinical evaluation. Methods: We analyzed death certificates from 1990-2023 from CDC Wonder Database. We used ICD-10 codes, C61 for malignant neoplasm of prostate and C56 for sepsis to identify related deaths. Mortality rates were compared by urbanization, sex and census region. Joinpoint Regression Program V5.4.0 computed Annual Percent Change with 95% CIs. p value < 0.05 was considered statistically significant. Results: Between 1999 and 2023, 39,801 deaths were recorded. Overall age-adjusted mortality rates (AAMRs) changed little over time, remaining near 2 deaths per 100,000 population (2.02 in 1999 and 2.00 in the most recent year). Clear differences were seen across demographic groups.In 1999, AAMRs among Black or African American was highest with value of 6.80 compared to white and hispanic or latino individual with AAMR vales 1.67 and 1.89 respectively.In 2023, mortality among Black individuals fell to 5.06; however, rates were still higher than those seen among White (1.76) and Hispanic/Latino (1.92) populations. Geographic differences were also evident.The mortality rate in the South, decreasing from 2.43 in 1999 to 2.16 in 2023, was highest among all the other census regions.Mortality rates declined across both metropolitan and nonmetropolitan areas, falling from 2.02 to 1.84 in metropolitan regions and from 2.05 to 1.73 in nonmetropolitan regions in year 2020. Conclusions: Overall sepsis-related mortality has remained relatively unchanged over the two decades, with significant racial and geographic disparities. Black individuals continue to experience disproportionately higher mortality, and Southern region showed consistently elevated rates. Both metropolitan and non-metropolitan areas saw modest declines. These findings highlight the continued need for targeted preventive measures and management strategies to reduce mortality and improve outcomes. Prostate cancer with sepsis AAMRs. variable AAMR 1999 AAMR 2023 Overall / Male 2.02 (1.91-2.14) 2.00 (1.92-2.09) Race Black or African American 6.80 (6.04-7.56) 5.06 (4.60-5.53) White 1.67 (1.56-1.78) 1.76 (1.67-1.85) Hispanic or Latino 1.89 (1.39-2.50) 1.92 (1.65-2.20) Census Region Northeast 2.25 (2.00-2.51) 1.99 (1.80-2.18) Midwest 1.71 (1.50-1.92) 1.65 (1.49-1.81) South 2.43 (2.22-2.63) 2.16 (2.02-2.30) West 1.54 (1.33-1.76) 2.12 (1.94-2.30) Urbanization AAMR 2020 Metro 2.02 (1.90-2.15) 1.84 (1.75-1.93) Non-metro 2.05 (1.79-2.30) 1.73 (1.54-1.92)