Dan Morgenstern-Kaplan

Background: SCLC remains an aggressive malignancy with limited therapeutic options after progression. Tarlatamab, a DLL3-directed bispecific T-cell engager, has a demonstrated survival benefit in clinical trials, but real-world data remain limited. We evaluated the safety, radiographic response, and treatment durability of Tarlatamab in a real-world cohort treated at a single academic center. Methods: We performed a retrospective review of patients with extensive-stage SCLC who received Tarlatamab at the University of Miami Sylvester Comprehensive Cancer Center between 2024 and 31 October 2025. Demographic, clinical, radiographic, and toxicity data were abstracted from electronic medical records. Radiographic response was defined as partial response or stable disease on follow-up imaging. PFS and overall survival OS were estimated using the Kaplan–Meier method. Results: Twenty-three patients were included (median age 72 years), of whom 61% were Hispanic and 61% had brain metastases prior to treatment. Forty-three percent had received two or more prior lines of therapy. CRS and ICANS occurred primarily during Cycle 1 and were limited to grade 1–2 events, with no grade ≥3 toxicities. Median time on treatment was 92 days with a median of four cycles. Among 18 evaluable patients, partial response was observed in 27.7% and stable disease in 16.7%, yielding a disease control rate of 44.4%. Median PFS was 139 days and median OS was 323 days (95% CI, 31–614). Conclusions: In a predominantly Hispanic, heavily pre-treated real-world population with high CNS disease burden, Tarlatamab demonstrated feasible administration, manageable immune-mediated toxicity, and clinically meaningful antitumor activity.

PURPOSE: Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by poor prognosis. The ADRIATIC trial demonstrated significant survival benefits with durvalumab as maintenance therapy for limited-stage SCLC (LS-SCLC). However, the high cost of durvalumab necessitates an evaluation of its cost-effectiveness. METHODS: A partitioned survival model was developed to assess the cost-effectiveness of durvalumab consolidation therapy compared with the standard of care (SOC). The model comprised three mutually exclusive health states: progression-free survival (PFS), progression of disease (POD)/metastasis, and death. Incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life year (QALY) gained, with a willingness-to-pay (WTP) threshold of $150,000 in US dollars (USD)/QALY. One-way and probabilistic sensitivity analyses were conducted. Analysis for POD was also stratified into intrathoracic, extrathoracic, and CNS. RESULTS: Durvalumab improved overall survival (OS) to 66.1 months and PFS to 40.2 months, compared with 57.8 and 31.8 months for SOC, respectively. The total cost of durvalumab was $163,722 USD versus $25,816 USD for placebo, resulting in an incremental cost of $137,905 USD. Durvalumab provided an incremental QALY gain of 0.36 years, yielding an ICER of $383,069 USD/QALY, exceeding WTP. On stratification, durvalumab in patients with extrathoracic progression nearly met WTP (ICER, $151,137 USD). CONCLUSION: Durvalumab remains cost-prohibitive for the overall cohort, exceeding acceptable thresholds despite favorable outcomes. Subgroup analysis, however, indicates that selective use in patients with extrathoracic progression may enhance cost-effectiveness. Overcoming economic barriers will be essential for the sustainable integration of immunotherapy into routine care.

PURPOSE: Variability in prostate cancer (PC) incidence and mortality reflects the substantial burden of the disease, shaped by factors such as socioeconomic variables, health care access, screening practices, and therapeutic treatments. This study assesses the trends in incidence, mortality, and disability-adjusted life years (DALYs) in PC among varying country income levels and WHO regions. METHODS: Global Burden of Disease Study database was used to extract age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs for PC among six WHO regions and four World Bank regions based on income levels from 1990 to 2019. Mortality-to-incidence ratios (MIRs) were computed. Joinpoint regression analysis was conducted to calculate the estimated annual percentage change. RESULTS: Between 1990 and 2019, ASIRs increased across all income level countries, with the greatest increase in the upper-middle–income countries (+64.7%). In the past 30 years, high-income countries have consistently observed the highest ASIR (2019: 77.5 per 100,000). High mortality rates were observed in low-income countries despite low ASIR overall. ASMRs increased in low-income countries (+14.3%), compared with a decrease in high- and upper-middle–income countries. DALYs also increased in low-income countries (+13.8%) compared with a decrease in high-income countries (–25.7%). MIRs decreased in all countries, with the largest decrease in high-income countries (–50%). In 2019, the highest MIR (1 per 100,000) was observed in low-income countries. CONCLUSION: The divergent trends in PC outcomes across income levels, such as a rise in mortality and DALYs in low-income countries, reflect global health care inequities that highlight the urgent unmet need for improving cancer screening, diagnosis, and treatment access in resource-limited settings.

Background: TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. Methods: Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Results: Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors. Conclusions: TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.

Immunization is an effective strategy to decrease hospitalization and mortality related to SARS-CoV-2. Since the introduction of mRNA-based SARS-CoV-2 vaccines (BNT1261b2 and mRNA-1273), several studies have outlined the immunogenicity and safety of these in hematopoietic stem cell transplant (HSCT) recipients. Herein, we describe the first systematic review and meta-analysis with pooled data of available evidence on SARS-CoV-2 vaccination in this patient population. We conducted a systematic review and meta-analysis of prospective cohort studies up to May 24 2022 in adult HSCT recipients who were vaccinated with ≥1 doses of either mRNA-based SARS-CoV-2 vaccine. The outcomes measured included: a) vaccine immunogenicity, b) safety, and c) breakthrough SARS-CoV-2 infections. Patients with solid organ transplant or prior documented history of SARS-CoV-2 infection were excluded. Pooled incidence of antibody positivity after one or more doses of mRNA-based SARS-CoV-2 vaccination in HSCT recipients mRNA-based SARS-CoV-2 vaccination was immunogenic in HSCT recipients, particularly among Auto-HSCT recipients. One or more doses of mRNA-based vaccine elicited a greater humoral response, compared to that of cellular immunity. Adverse events were common, but often were mild. Breakthrough infections are rare after ≥ 1 doses. John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bonds

Bosutinib is a breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitor (TKI) used for the treatment of chronic myeloid leukemia (CML). Patients on TKIs may develop severe cutaneous adverse reactions (SCARs). A 73-year-old female with CML treated with a second-generation TKI (bosutinib) was evaluated after developing fever and a maculopapular exanthema with skin-peeling affecting her lips, oral mucosa, and genitals 10 days after starting the medication. She required hospitalization, bosutinib discontinuation, and management with intravenous corticosteroids and antibiotics. Patch testing was contraindicated due to the severity of the reaction. The patient was subsequently challenged with first-generation TKI along with careful observation without any adverse reactions. She has not reported any adverse reactions while on therapy in the last two years. In patients who have suffered from SCARs, the suspected triggers must be avoided in all instances. In some cases, the underlying condition limits the use of alternative agents, but low-concentration patch testing may help guide alternative therapies within the same medication group. There appears to be a low cross-reactivity among generational TKIs, and our patient benefited from treatment with a structurally dissimilar alternative TKI for her CML.