Aziz, Nouman

e20551 Background: Lung cancer is leading cause of cancer related mortality globally, with non-small cell lung cancer (NSCLC) comprising approximately 80% of all cases. The combination of immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1), specifically Durvalumab, and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors, such as Tremelimumab has demonstrated clinical efficacy in both adjuvant and neoadjuvant settings. However, a comprehensive systematic review of the available data is currently lacking. This study aims to assess the therapeutic efficacy of Durvalumab combined with Tremelimumab in NSCLC focusing on key end points including progression-free survival, overall survival, overall response rate, and safety, with particular attention to any adverse events and mortality. Methods: A comprehensive literature search was performed to identify relevant studies published until March 2024 across PubMed, Google Scholar, and Embase databases. Outcomes were pooled using the random effects DerSimonian-Laird model and reported as hazard ratio (HR) with a 95% confidence interval. A p-value of less than 0.05 was considered statistically significant. Results: A total of 1600 patients with NSCLC were included in the analysis, with 825 patients receiving Durvalumab plus Tremelimumab, and 775 patient receiving Standard chemotherapy across four studies. For Efficacy, following parameters were statistically significant: Progression Free Survival HR 0.75, 95%CI: 0.59, 0.92; Overall Survival HR 0.8, 95%CI: 0.58, 0.99; Overall Response Rate HR: 0.68, 95%CI: 0.47, 0.88, Mean Duration of Response was 12.23 month. Safety outcomes revealed that Durvalumab plus Tremelimumab versus Standard chemotherapy were comparable in mean percentage in terms of following parameters: Any Adverse Event (85.1% vs 92.8%), Any Serious Adverse Event (28.9% vs 17.75%), any mortality (6.35% vs 3.4%), Adverse Event leading to discontinuation (11.6% vs 10.13%), Any treatment related adverse event (69.96% vs 85.6%) and Any Treatment Related Death (0.9% vs 0.3%). Conclusions: Efficacy outcomes in patients treated with Durvalumab plus Tremelimumab demonstrated clinically meaningful improvements while the safety profile was comparable to that of Standard chemotherapy. Given the increasing use of this combination therapy as adjuvant and neoadjuvant treatment for NSCLC, further clinical trials are warranted to confirm and validate these findings.

e20593 Background: Tislelizumab, an anti-PD-1 antibody, is emerging as a promising immunotherapy agent and has demonstrated clinical benefit and acceptable tolerability in recent lung cancer trials. This study aims to assess the safety and efficacy of Tislelizumab, as monotherapy or combined with chemotherapy (Group 1), as a superior treatment alternative for lung cancer compared to standard chemotherapy (Group 2) in improving patient outcomes. Methods: Following PRISMA guidelines, a systematic search was conducted through MEDLINE, Embase, Scopus, Science Direct, Cochrane (CENTRAL), and ClinicalTrials.gov from inception to December 2024 to identify Randomized Control Trials (RCTs). Hazards ratio (HRs) and risk ratios (RRs) were generated, by employing a Random-effects model with a 95% confidence interval (CI). Statistical analysis was performed using RevMan 5.4, with statistical significance set at p<0.05. Our outcomes of interest were Progression Free Survival (PFS), Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of response (DOR), and treatment-related adverse Events. Results: A total of 6 RCTs involving 2107 patients were included for analysis. Pooled analysis demonstrated that Group 1 significantly improved PFS, OS, and DOR with HRs of 1.85 (95% CI: 1.71-1.99; p <0.00001, I² = 0%), 2.01 (95% CI: 1.75-2.29; p <0.00001, I² = 0%) and 2.14 (95% CI: 1.52-3.03; p <0.0001, I² = 39%), respectively. Group 1 has better DCR and ORR compared to Group 2 with RRs of 1.52 (95% CI: 1.12-2.07; p= 0.007, I² = 97%) and 1.50 (95% CI: 1.20-1.86; p= 0.0003, I² = 83%), respectively. The high heterogeneity observed in the pooled analysis of DCR (I² = 97%) and ORR (I² = 83%) likely reflects variability in study populations, treatment protocols, and response assessment criteria across the included RCTs. Subgroup or sensitivity analyses could help identify contributing factors. Despite the heterogeneity, the pooled effect sizes indicate a statistically significant improvement in DCR and ORR with Tislelizumab, with caution warranted when generalizing these findings. Group 1 significantly reduced all-cause mortality compared to Group 2 (RR = 0.89; 95% CI: 0.83–0.95; p = 0.0003), with no heterogeneity (I² = 0%). No significant differences were found in adverse events, except for ALT elevations. (RR = 1.36; 95% CI: 1.14–1.61; p = 0.0006, I² = 25%). Conclusions: Tislelizumab, with or without chemotherapy, demonstrates greater PFS and OS benefits compared to chemotherapy alone in patients with lung cancer. There was a significantly reduced all-cause mortality in the intervention group; however, the observed increase in the risk of ALT elevation underscores the need for vigilant liver function monitoring. When combined with chemotherapy, Tislelizumab presents a promising treatment option for lung cancer.