Malik, Haris Mumtaz

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.

e17089 Background: Prostate cancer (PC) is often treated with androgen-deprivation therapy (ADT), but progression remains a challenge. Darolutamide, a next-generation androgen receptor inhibitor, may improve outcomes when combined with ADT. This systematic review and meta-analysis evaluates the efficacy and safety of darolutamide plus ADT in hormone-sensitive (HSPC) and castration-resistant prostate cancer (CRPC). Methods: A comprehensive search of PubMed, Cochrane, Clinicaltrials.gov, Embase, and Scopus was conducted through January 11, 2025. Randomized controlled trials (RCTs) comparing darolutamide plus ADT vs. placebo or control in prostate cancer were included. Data on overall survival, metastatic progression, antineoplastic therapy initiation, pain progression, bone fractures, hypertension, adverse events and serious adverse events were analyzed. Outcomes were pooled as risk ratios (RR) with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed via Higgins I², with subgroup analyses for HSPC and CRPC. Results: Four RCTs with 4,992 patients (darolutamide + ADT=3007; control=1985) were further included for quantitative analysis. Our pooled analysis showed a statistically significant decrease in the development of metastatic CRPC across both HSPC and CRPC (RR: 0.38 [0.19, 0.77], p=0.007). Similarly, progression to pain (RR: 0.81 [0.71, 0.92], p=0.001) and the use of antineoplastic therapy (RR: 0.46 [0.38, 0.57], p<0.0001) was significantly delayed across all PC, indicating slower disease progression. While a slightly higher overall survival was noted in the CRPC subgroup (RR: 1.08 [1.01, 1.14], p=0.007), no significant differences were reported on the use of combination therapy across HSPC and overall PC (RR: 0.71 [0.39, 1.31], p=0.28). While a significantly higher risk of developing adverse events (RR: 1.08 [1.03, 1.14], p=0.002) and serious adverse events (RR:1.2 [0.99, 1.45], p=0.07) was noted in the CRPC subgroup, a slight increase was reported in the overall cohort and HSPC, although with statistical insignificance. Bone fractures (RR: 1.52 [1.12, 2.07], p=0.008) and hypertension risk (RR: 1.28 [1.03, 1.59], p=0.03) were elevated, while rates of rash, fatigue, falls, and mental impairment were similar. Conclusions: Combination therapy of darolutamide and ADT reduced metastatic progression and slowed tumor growth but did not significantly improve overall survival. Adverse events were more common, particularly in CRPC cohort. Longer follow-up studies are needed to assess long-term efficacy and weigh tumor control against adverse event risks.