Gandicheruvu, Haritha

e20511 Background: Trop-2 ADCs have emerged as a novel therapeutic approach in NSCLC that is refractory to chemotherapy and immune checkpoint inhibitors. Comparative interpretation of the efficacy of multiple Trop-2 ADCs, including Sacituzumab tirumotecan (Sac-TMT), Datopotamab deruxtecan (Dato-DXd), and Sacituzumab govitecan (SG), is limited. We therefore conducted a systematic review, IPD survival analysis, and meta-analysis to evaluate the efficacy and PROs of Trop-2 ADCs compared with chemotherapy in NSCLC. Methods: A systematic search was conducted from inception to October 31, 2025, across PubMed, Scopus, Cochrane, and CT.gov. Clinical trials evaluating Overall Survival (OS) and Progression-free survival (PFS) in patients treated with Trop-2 ADC alone or compared with Chemotherapy were included. IPD were extracted from the Kaplan-Meier curves of clinical trials for reconstruction using the KMfromIPD website by MD Anderson, which stratified the data by treatment group. Outcomes included OS, PFS, and time to deterioration (TTD). The cumulative data were analyzed using R 4.5.1 and RStudio. RevMan version 5.4.1 was used for the meta-analysis of subgroups. Heterogeneity was assessed using the I 2 statistic. Results: Of 513 articles, 7 phase 1/2 single-arm and 4 randomized control trials were included, comprising 2,619 patients.Trop-2 ADCs were associated with improved OS (Median 15.6 vs 12.5 months; HR 0.78, 95% CI 0.69-0.88; p < 0.0001) and PFS (Median 5.5 vs 4.1 months; HR 0.66, 95% CI 0.59-0.74; p < 0.0001). Sac-TMT demonstrated the greatest OS benefit (OS 23.3 months; HR 0.40). Further drug classes are depicted in Table 1. PROs assessment showed TROP-2 ADCs were associated with longer time to deterioration in global quality of life and dyspnea-free survival compared to chemotherapy (HR 0.8 and 0.69), (p = 0.04 and p < 0.0001, respectively). Exploratory subgroup analysis showed improved OS among patients with actionable gene alteration (AGA) treated with Trop-2 ADCs (HR 0.58, p < 0.00001). However, no significant difference was observed in either treatment arm among patients without AGA (HR 0.89, p = 0.15). Conclusions: Trop-2 ADCs were associated with improved survival and PROs compared with chemotherapy in NSCLC, with variability across agents. Sac-TMT has shown higher OS and PFS. Dato Dxd had a favorable PFS; however, the OS was not superior to chemo. Furthermore, SG showed no favorable clinical outcomes compared with the chemo group. These findings support the continued development of Trop-2-directed therapies and highlight the need for prospective comparative trials and biomarker-driven patient selection. Drug N mOS (months) HR p- value mPFS (months) HR p- value Sac-TMT 386 23.32 0.4 <0.000001 7.5 0.5 <0.000001 Dato-DXd 486 13.2 0.95 0.55 5.02 0.71 <0.000001 SG 347 12.61 1.02 0.82 4.18 0.87 0.05

58 Background: Skeletal-related events (SREs) are a common cause of morbidity and mortality in metastatic castration-resistant prostate cancer (mCRPC). These complications are managed using bone-modifying agents (BMAs), radiation therapy, and surgery, and lead to diminished quality of life irrespective of their castration status. We sought to evaluate the mortality trends for patients with PC and SREs in patients of >65 years from 1999 to 2023 using the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database. Methods: The database was searched from January 1, 1999, to December 31, 2023. Mortality trends were assessed by identifying prostate cancer international classification of diseases-10th revision code (ICD-10 code C61) as the underlying cause of death in individuals aged >65 years, and (SREs) as contributing causes using the following ICD-10 codes: S02, S12, S22, S32, S42, S52, S62, S82, S92, T02, T08, T10, T12, T14.2, Y93.2, E55, M80, M81, M84.4. Joinpoint 5.0 software was used to analyze mortality trends. Results: From 1999 to 2023, a total of 3,231 deaths were reported. Trend analysis revealed a decline in overall mortality from 1999 to 2014, with an annual percentage change (APC) of -1.60 (CI: -2.6, -0.5; p = 0.005), followed by a significant increase in mortality from 2015 to 2023, with an APC of 5.30 (p = 0.0001). When stratified by age, individuals aged 65-69 showed an insignificant decline in mortality over the entire study period. For those aged 70-74, mortality significantly decreased from 1999 to 2014 (APC: -3.02, CI: -5.0, -0.9; p = 0.008), but experienced an exponential increase from 2014 to 2023 (APC: 14.07, CI: 8.7, 19.6; p = 0.00005). In the 75-79 age group, mortality significantly decreased from 1999 to 2011 (APC: -5.6, CI: -9.5, -1.6; p = 0.0091), followed by a robust increase from 2011 to 2023 (APC: 7.06, CI: 2.7, 11.5; p = 0.002). For individuals aged >80 years, the trend showed an insignificant decline in mortality from 1999 to 2023 (APC: -0.260, CI: -0.8, 0.3; p = 0.380). Conclusions: Our study revealed significant trends in prostate cancer mortality attributable to SREs, contributing to a sharp increase from 2015 to 2023. Age-stratified analysis revealed that substantial mortality is reported in patients aged 70-79, with the most pronounced rise occurring after 2014. These findings emphasize the growing burden of SREs in older prostate cancer patients, underscoring the need for targeted interventions along with a focus on patient-reported outcomes to improve survival and quality of life.

Abstract Background: B-cell acute lymphoblastic leukemia (B-ALL) accounts for 0.3% of all new cancer cases and 0.2% of cancer-related deaths in the United States. While survival outcomes have improved over the years, further intensifying chemotherapy has offered diminishing returns. Blinatumomab, a bispecific T-cell engager targeting CD3 and CD19, has shown clinical benefit in minimal residual disease (MRD)-positive and relapsed/refractory settings. Its recent FDA approval for use in the consolidation phase of newly diagnosed Philadelphia chromosome–negative, CD19-positive B-ALL followed the landmark E1910 trial, which demonstrated a survival advantage when added to standard chemotherapy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blinatumomab in the consolidation phase across clinical trials and real-world studies. Methods: A comprehensive review was carried out on PubMed, Clinicaltrials.gov and Cochrane library from inception up to July 2025 using the terms “Blinatumomab” and “ALL”. Studies that evaluated response: overall response rate (ORR) and complete response (CR) and adverse events between Blinatumomab and control groups were included. Out of the 19 studies that met the inclusion criteria, 12 were clinical trials and 7 were observational studies. Open meta-analyst software was used to analyze the data. For single arm study, PLO (logit-transformed proportion) was used as a metric. Der Simonian-Laird random effects model was used to generate forest plots of pooled response rate estimates and 95% CI along with p-values and I2 statistics for heterogeneity. Results: A total of 824 patients were included (54.4% male, 45.6% female), with a median age of 48 years. The median follow-up across studies was 18.2 months (range, 3.4 to 92.8 months). Pooled ORR was 96.4% (95% CI, 93–98; p=0.955), and pooled CR was 92.7% (95% CI, 87–95; p&lt;0.001). TRAEs leading to treatment discontinuation occurred in 6.8% (95% CI, 2.5–11.2; p=0.004), dose reductions in 2.9% (95% CI, 0.2–5.6; p=0.069), and treatment-related mortality in 1.4% (95% CI, 0.4–2.3; p=0.256). There was moderate heterogeneity across studies for toxicity outcomes. Conclusion: Consolidation-phase blinatumomab is associated with high response rates and a favorable safety profile, reinforcing the survival gains observed in E1910 (3-year OS: 83% vs 65%). With low rates of treatment-limiting toxicity and mortality, our findings support the incorporation of blinatumomab into standard adult B-ALL consolidation regimens. These data suggest that this immunotherapeutic approach may help narrow the outcome gap between adult and pediatric ALL.