Habib, Huzefa

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.

e20139 Background: Extensive-stage small cell lung cancer (ES-SCLC) frequently presents with brain metastases, affecting approximately 20% of the patients at diagnosis. The prognostic impact of baseline brain metastases on survival outcomes in patients treated with contemporary chemo-immunotherapy remains unclear, creating uncertainty in first-line treatment selection for this high-risk population. We conducted a systematic review and meta-analysis to evaluate the impact of baseline brain metastases on treatment outcomes in ES-SCLC. Methods: This PRISMA-compliant systematic review and meta-analysis was prospectively registered in PROSPERO. PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were systematically searched from database inception through January 2026 to identify randomized controlled trials evaluating PD-1/PD-L1-based chemo-immunotherapy versus platinum-etoposide chemotherapy in adults with ES-SCLC. Two reviewers independently screened studies and extracted data, with discrepancies resolved by consensus. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled separately for patients with baseline brain metastases (BM+) and without brain metastases (BM−) using random-effects models with Hartung–Knapp adjustment. Analyses were performed using R. Prespecified subgroup analyses were conducted based on follow-up duration and immunotherapy regimen. Results: Twelve randomized controlled trials were included. Among patients with baseline brain metastases (BM+), pooled OS from seven studies did not show a significant survival benefit (HR 0.84, 95% CI 0.66–1.08, I² = 0.0%, P = 0.145), nor did pooled PFS from five studies (HR 1.03, 95% CI 0.60–1.79, I² = 0.0%). Subgroup analyses revealed no significant heterogeneity. In contrast, among patients without baseline brain metastases (BM−), pooled OS from nine studies demonstrated a significant survival benefit (HR 0.72, 95% CI 0.69–0.76, I² = 0.0%, P < 0.001), with corresponding improvement in PFS (HR 0.70, 95% CI 0.60–0.82, I² = 0.0%). These findings indicate a differential treatment effect according to baseline brain metastasis status. Conclusions: First-line chemo-immunotherapy does not apprear to confer a significant survival benefit in ES-SCLC patients with baseline brain metastases, reflecting a differential treatment effect by brain metastasis status. These findings suggest that baseline brain metastases should be considered in treatment selection and future clinical trial design and highlight the need for optimized systemic strategies for this high-risk population.