Aslam, Raza

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.

e19022 Background: Chronic lymphocytic leukemia (CLL) is a common adult leukemia that originates by dysfunctional development of the lymphocytes. Acalabrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, has demonstrated promising outcomes as a targeted therapy alternative to chemoimmunotherapy for treating CLL. The objective of this retrospective analysis was to compare the safety profiles of acalabrutinib and chemoimmunotherapy in patients with CLL and to evaluate the potential of acalabrutinib as an alternative therapeutic option. Methods: We conducted a retrospective cohort analysis using the TriNetX platform analyzing data of patients diagnosed with CLL from January, 2000 to January, 2025. Data was classified into cohorts on the basis of treatment with either acalabrutinib or chemoimmunotherapy. Propensity score matching analysis was carried out to balance their demographic and clinical characteristics. Demographic factors included age (≥18 years), sex, race, and ethnicity. Outcomes assessed included all cause death, atrial fibrillation, hypertension, acute heart failure, ventricular arrythmias, and bleeding. Kaplan-Meier survival analysis was employed. Results: A total of 4,006 patients were included in the analysis, 847 received acalabrutinib and 3,172 underwent chemoimmunotherapy, with a mean age of 70±11 and 69±14 years respectively. Participants were mostly male, with the majority of the patients being non-Hispanic Whites. Median period of follow up was 578 and 925 days respectively, incidence and risk of mortality and adverse events were assessed. A lower risk of mortality was noted with acalabrutinib (RR: 0.407; 95%CI: 0.32, 0.51; p<0.0001). Additionally, atrial fibrillation developed in fewer than 10 patients on use of acalabrutinib, thus carrying significantly lower odds (odds ratio (OR):0.3; 95%CI: 0.16, 0.58; p=0.001) than chemoimmunotherapy, which reported atrial fibrillation in 120 patients. Similarly, significantly lesser incidence of hypertension was noted on use of acalabrutinib, implying safer drug profile. Bleeding risk was also reduced in the acalabrutinib cohort and was statistically significant (OR:0.36, 95%CI: 0.24, 0.52; p<0.0001). The odds of acute heart failure (OR:1.25, 95%CI: 0.61, 2.57; p=0.54) and ventricular arrhythmia (OR:1.5, 95%CI: 0.72, 3.14; p=0.2) were statistically nonsignificant. Conclusions: The use of acalabrutinib in patients with CLL was associated with statistically significant better safety profile, with lesser risk of mortality, bleeding events and atrial fibrillation. Clinicians may consider using acalabrutinib as a superior treatment modality in the treatment of CLL. Further research maybe required to optimize treatment protocols in the best interest of patients.