Haider, Faseeh

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.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.