Citations

TPS10057 Background: Ewing sarcoma (EWS) is an aggressive tumor of the bone and soft tissue primarily affecting adolescents and young adults. For patients with recurrent disease, outcomes remain poor with 5-year survival rates of 10%–15%, highlighting the need for novel approaches. STEAP1 is highly expressed in EWS cell lines, xenograft models, and patient tumor samples 1 and is transcriptionally regulated by EWSR1::FLI1 , the main oncogenic driver in EWS. Xaluritamig, a humanized bispecific XmAb 2+1 T-cell engager targeting STEAP1 and CD3, has demonstrated potent, antigen-dependent T-cell–mediated lysis of STEAP1-expressing EWS cell lines 1 and induced robust in vivo antitumor activity in EWS xenograft models with concomitant CD8+ T-cell activation. In metastatic castration-resistant prostate cancer, another STEAP1-expressing solid malignancy, xaluritamig has shown meaningful antitumor activity and a manageable safety profile 2 supporting its clinical evaluation in R/R EWS. Methods: This ongoing, phase 1b, single-arm, open-label, two-part, multicenter study (NCT07297979) is evaluating xaluritamig in pediatric, adolescent, and adult patients with a histologic diagnosis of EWS and an EWSR1 :: ETS fusion gene locally confirmed by next-generation sequencing. Patients must have R/R EWS following ≥1 line of systemic therapy and Karnofsky or Lansky performance status ≥70. Part 1 (dose confirmation) consists of cohort 1 (age ≥12 years) and cohort 2 (age ≥2 to <12 years), and part 2 (dose expansion) includes patients aged ≥2 years with no upper age limit at enrollment. This study includes a 21-day screening period, a treatment period, a safety follow-up period, and a long-term follow-up period. Patients receive xaluritamig every 2 weeks once reaching the target dose until radiographic disease progression per RECIST v1.1, clinical disease progression, unacceptable toxicity, initiation of other anticancer therapy not permitted per protocol, withdrawal of consent, death, or end of study as determined by the sponsor, whichever is earlier. Primary endpoints are safety, tolerability, and determination of recommended dose(s) for expansion. Secondary endpoints are pharmacokinetics, preliminary antitumor activity, and immunogenicity. Biomarker evaluation as an exploratory endpoint includes assessment of serum cytokines, other pro-inflammatory markers, immune-cell subsets, circulating tumor DNA, STEAP1 protein expression, and tumor genomic profile and their association with safety and efficacy. CRS mitigation plan includes step-up dosing, steroid premedication, and administration of interleukin-6 inhibitors as needed. Site activation commenced in January 2026 and enrollment is ongoing. 1. Nolan-Stevaux O. Cancer Res. 2020;80(16_Suppl):DDT02–03. 2. Kelly WK, Danila DC, Lin CC, et al. Cancer Discov . 2024;14(1):76-89. Clinical trial information: NCT07297979 .

e24201 Background: Anthracyclines remain curative in many pediatric and adolescent/young adult (AYA) cancers but confer dose-dependent cardiotoxicity. Dexrazoxane reduces cardiac injury; however, concerns persist regarding potential impact on oncologic outcomes. Methods: We conducted a PRISMA-compliant systematic review and meta-analysis of studies comparing anthracycline therapy with versus without dexrazoxane in pediatric/AYA populations. Databases included MEDLINE, Embase, and CENTRAL. Outcomes included cardiac function (LVEF decline, clinical heart failure), event-free survival (EFS), overall survival (OS), relapse, and second malignant neoplasms (SMN). Random-effects meta-analysis pooled hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for binary endpoints. Results: Twelve studies with 1,384 patients were included. Dexrazoxane significantly reduced risk of clinical heart failure (RR 0.34, 95% CI 0.21–0.55) and preserved LVEF compared with controls. No significant differences were observed in EFS (HR 0.97, 95% CI 0.84–1.12), OS (HR 0.95, 95% CI 0.81–1.11), relapse (RR 1.02, 95% CI 0.87–1.19), or SMN incidence (RR 1.05, 95% CI 0.78–1.41). Benefits were consistent across cancer types, cumulative anthracycline doses, and follow-up durations. Conclusions: Dexrazoxane provides substantial cardio protection in pediatric and AYA patients receiving anthracyclines without compromising oncologic outcomes or increasing risk of SMNs. Clinical Takeaway: Routine incorporation of dexrazoxane in high-risk anthracycline regimens can prevent cardiotoxicity while maintaining curative potential.

e24198 Background: Even when radiotherapy is delivered outpatient, treatment-related nausea, vomiting, and dehydration can precipitate hospitalization, driving cost and morbidity. National estimates of this burden are limited. Methods: We analyzed the HCUP National Inpatient Sample (NIS) for 2016–2022 to identify hospitalizations with radiotherapy encounters (Z51.0) and concurrent diagnoses of nausea, vomiting, or dehydration using ICD-10 codes. Outcomes included length of stay (LOS), total charges, ICU use proxies, in-hospital mortality, and non-home discharge. Survey-weighted national estimates were calculated, and multivariable regression assessed predictors including cancer site proxies, age, comorbidity burden, insurance status, income quartile, and hospital characteristics. Results: Across 7,842 weighted admissions, mean LOS was 4.6 days (SD 2.1), mean total charges $23,400 (SD $8,700), and ICU-level care proxies were required in 12% of admissions. In-hospital mortality was 0.9%, and 21% of patients required non-home discharge. Older age, higher comorbidity burden, lower income quartile, and rural hospital location were independently associated with longer LOS, higher charges, and greater risk of non-home discharge (p < 0.01). Admissions for gastrointestinal or head/neck malignancies had the highest rates of RINV-related hospitalization. Temporal trends showed stable rates over the 7-year period. Conclusions: Hospitalizations for RINV and dehydration during radiotherapy represent a measurable national burden with disparities by socioeconomic status, tumor site, and hospital location. Clinical Takeaway: Targeted outpatient supportive interventions, particularly for high-risk patients, may reduce hospitalization, costs, and morbidity during radiotherapy.

e24196 Background: Radiation-induced edema and necrosis are common, dose-limiting toxicities. Corticosteroids remain first-line therapy but are associated with significant morbidity and limited long-term tolerability. Dietary and herbal agents with antioxidant, anti-inflammatory, and neurovascular protective properties are suggested as adjunct or steroid-sparing agents, yet systematic analysis of their overall efficacy is unclear. Methods: A systematic search of PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from inception through December 2025. Eligible studies included randomized trials and observational studies evaluating non-traditional dietary or herbal interventions for radiation-induced cerebral edema or injury. The primary outcome was radiographic improvement of cerebral edema on MRI, harmonized as any MRI-documented reduction or resolution of edema or necrosis. A random-effects comparative meta-analysis was performed for controlled studies with extractable binary outcomes, excluding case reports. A secondary random-effects, single-arm meta-analysis of proportions was conducted for Boswellia serrata , including observational cohorts and case series. Studies without MRI-based cerebral toxicity endpoints were synthesized qualitatively. Results: Eleven studies encompassing more than 400 patients met the inclusion criteria. Boswellia serrata was the most frequently evaluated intervention, followed by dl-3-n-butylphthalide, vitamin E, omega-3 fatty acids, melatonin, multi-herbal formulations, and integrative multi-compound regimens. In a comparative meta-analysis of two controlled studies, dietary and herbal interventions were associated with a significantly higher likelihood of radiographic improvement in cerebral edema compared with standard therapy or placebo (pooled risk ratio 1.60, 95% CI 1.12–2.30; I² = 0%). In a secondary, single-arm, meta-analysis of five Boswellia serrata studies, the pooled radiographic response rate was 56.2% (95% CI 45.0%–67.1%). Across other studies, neurologic and cognitive improvement and steroid-sparing effects were commonly reported, while serious treatment-related adverse events were uncommon. Integrative oncology approaches combining Boswellia serrata with other natural compounds were also associated with improved survival and reduced steroid dependence in longitudinal observational studies. Conclusions: Dietary and herbal interventions, particularly Boswellia serrata , are associated with meaningful radiographic and clinical improvement in radiation-induced cerebral edema and brain injury, with favorable safety profiles. These findings support further prospective randomized trials and suggest a potential adjunctive role for non-pharmacologic therapies in managing radiation-related neurotoxicity.

e24182 Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a clinically significant complication of anticancer treatments, including anthracyclines and trastuzumab, often necessitating dose reduction or discontinuation of potentially life-saving therapy. While angiotensin receptor-neprilysin inhibitors (ARNI) have demonstrated mortality and hospitalization benefits in heart failure with reduced ejection fraction, their efficacy in preventing chemotherapy-induced cardiotoxicity remains controversial due to conflicting results and a lack of large-scale data. Therefore, we performed a meta-analysis to evaluate the efficacy of ARNI for the prevention of cardiotoxicity in patients receiving chemotherapy. Methods: We searched PubMed, Embase, and Cochrane Central from intercept till 17 December 2025 for studies evaluating the benefit of ARNI in preventing CTRCD among patients undergoing cardiotoxic cancer therapy. The primary outcomes assessed were changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T. Statistical analysis was performed using Review Manager, and heterogeneity was assessed using the I2 statistic. The study protocol was registered with PROSPERO (CRD420251266270). Results: A total of 442 patients from four RCTs were included, with follow-up periods ranging from 6 to 18 months. The analysis of changes in LVEF showed a trend toward improvement (mean difference 1.18; 95% CI -0.04 to 2.40; p = 0.06), though this did not reach statistical significance. There were no statistically significant differences observed in changes in GLS (mean difference -0.94; 95% CI -2.43 to 0.55; p = 0.14), NT-proBNP (mean difference -0.94; 95% CI -9.57 to 7.70; p = 0.69), or troponin T (mean difference 0.06; 95% CI -1.13 to 1.26; p = 0.92). Conclusions: In conclusion, prophylactic treatment with ARNI in patients undergoing cardiotoxic cancer therapy did not result in statistically significant changes in LVEF, GLS, or cardiac biomarkers (NT-proBNP and troponin T), although a non-significant trend toward preserved LVEF was observed. The lack of statistical significance may be attributable to limited statistical power due to small sample sizes and heterogeneity across cancer therapies. Given the observed trend in LVEF preservation, further adequately powered, large-scale RCTs focusing on specific chemotherapy regimens are needed.

e24165 Background: Taxanes are associated with a higher incidence of immediate hypersensitivity reactions (HSRs) compared to other classes of chemotherapeutic agents, even with adequate premedication. This study evaluates whether a titrated infusion protocol reduces the rate of first-dose HSRs to taxanes. Methods: This was a retrospective cohort study conducted at a single site hematology/oncology infusion center. The fixed-rate arm consisted of patients from January 2022 to July 2023 who received a fixed infusion rate for their first dose. The titration arm comprised patients from August 2023 to July 2024 who underwent a three-step titration protocol for their first dose. The primary endpoint was the rate of immediate HSRs during the first lifetime dose of docetaxel or paclitaxel. Secondary endpoints included HSR severity, HSRs during the first or second dose, and rate of treatment discontinuation due to HSRs. Results: Of 479 patients included (240 fixed-rate; 239 titration), HSRs occurred in 7.1% of the fixed-rate group and 11.3% of the titration group (OR 1.67, 95% CI 0.89-3.15; p= 0.1104). There were no differences in the severity of HSRs or in the rate of treatment discontinuation among both groups. Conclusions: The use of a titrated infusion protocol for first lifetime dose taxanes did not significantly reduce the incidence or severity of immediate HSRs. These findings suggest that a titration protocol may not confer additional benefits over fixed-rate in this setting. Primary and secondary endpoints. Fixed (N=240) Titration (N=239) OR 95% CI p-value Primary Endpoint Rates of immediate HSR 17 (7.1%) 27 (11.3%) 1.67 0.89- 3.15 0.110 Secondary Endpoints Severity of immediate HSR N=17 N=27 Grade 1 10 (58.8%) 8 (30.8%) 0.637 Grade 2 6 (35.3%) 12 (46.2%) 0.157 Grade 3 1 (5.9%) 6 (23.1%) 0.059 Rates of immediate HSR with first or second dose combined N=471 infusions N=453 infusions 26 (5.5%) 37 (8.2%) 1.52 0.91-2.56 0.111 Taxane administration time (min) N=239 N=232 1-hour infusion 71.8 92.8 3-hour infusion 187.6 201.6 Rates of medication discontinuation due to immediate HSR N=26 N=37 1 (3.8%) 8 (21.6%) 6.90 0.81-59.17 0.069

e24122 Background: Using multiple channels and theory-based recruitment messaging are strategies to enroll diverse audiences in cancer clinical trials (CCTs) and reducing sociodemographic health disparities. 1-7 Customizing recruitment content to participants, such as including race-concordant images (i.e., images that match participants race/ethnicity) and translating information to a community-level (i.e., message framing) is linked to positive health-seeking behavior among minorities and their intention to enroll in clinical trials. 8,9 Drawing on Communication Accommodation Theory and social identity theories, this paper evaluated recruitment channels used to successfully enroll underrepresented participants in CCTs, and preferences for race-concordant images and message framing. Methods: Social media ads, flyers, and postcards were used to recruit rural, African American/Black, and Hispanic adults interested in cancer prevention and screening. Participants ( N = 430, M = 40 years old, SD = 14.47, range 18-85) were recruited to the study with unique links to track the stimuli they viewed, and demographics were collected. Participants viewed one of four images and one of two motivational recruitment message frames. Specifically, given our interest in recruiting rural, African American/Black, and Hispanic populations to CCTs, three images were selected to feature each population, and a fourth Inclusive image featuring all three. Additionally, the person-centered message frame conveyed participating in research is motivated by one’s own benefit, whereas the other-centered frame conveyed motivation for other people’s benefit. Results: In social media ads, across a three-week campaign there were 2,653 clicks on recruitment stimuli ads, resulting in a 6.17% response rate of recruited and enrolled. Across all recruitment channels, enrolled participants engaged with the Inclusive (n = 202) and Black/African American (n = 130) recruitment stimuli the most. In the case of framing, person- (n = 174) and other-centered (n = 199) had similar engagement. Investigating within-race preferences, a chi-square analyses revealed Black/African American participants preference for Inclusive (n = 172) and Black/African American (n = 109) visuals over Hispanic (n = 13) and Rural (n = 17), X 2 (30, N = 419) = 194.94, p < .001; as well as preference for other-centered (n = 180) vs person-centered (n = 129) framing, X 2 (30, N = 419) = 183.95, p < .001. Conclusions: Our findings indicate that Black/African American participants are more likely to interact with race-concordant or sociodemographic inclusive stimuli, and a preference for other-oriented framing. To reduce health disparities in CCT participation, recruitment must avoid monolithic approaches and instead segment outreach by sociolinguistic and social identity factors.

e24089 Background: Pancreatic cancer is associated with high symptom burden and frequent acute care utilization. Although early palliative care improves quality of life in advanced malignancies, real-world data describing its timing and downstream impact in pancreatic cancer remain limited. Methods: We conducted a retrospective cohort study using Epic Cosmos (2015–2025). Adults (≥18 years) with pancreatic cancer were identified using ICD-10 code C25.*. Early palliative care was defined as a documented palliative care encounter (ICD-10 Z51.5) within 0–2 months of cancer diagnosis. Patients were categorized as early palliative care versus not-early palliative care (late or no palliative care). A landmark approach was applied, with outcomes assessed beginning 2 months after diagnosis to mitigate immortal time bias. Outcomes included opioid use, antiemetic use, occupational/physical therapy (OT/PT) utilization, emergency department (ED) encounters resulting in inpatient admission, and inpatient length of stay. Results: Among 4,641 patients with pancreatic cancer, 464 (10.0%) received early palliative care, 365 (7.9%) received palliative care later, and 3,812 (82.1%) had no documented palliative care encounter. Compared with patients without early palliative care, early palliative care recipients demonstrated higher utilization of symptom-directed interventions, including opioids (40.6% vs 22.5%), antiemetics (37.2% vs 20.3%), and occupational/physical therapy services (6.2% vs 3.2%). Early palliative care was associated with a higher proportion of emergency department encounters resulting in inpatient admission (52.5% vs 23.6%), consistent with earlier consolidation of symptom-driven care. Mean inpatient length of stay was similar between groups (6.0 vs 6.2 days). Overall survival appeared comparable between groups; however, survival estimates in EHR-based analyses are limited by residual confounding and timing constraints. Conclusions: In a large national EHR cohort, early palliative care within two months of pancreatic cancer diagnosis was infrequently used but was associated with greater engagement in symptom-directed medications and supportive services, as well as a distinct downstream pattern of acute care utilization. These findings suggest that earlier integration of palliative care may improve coordination of symptom-focused care and represent an actionable quality-of-care target in pancreatic cancer.

e24088 Background: Chemotherapy-induced nausea and vomiting (CINV) significantly affects treatment tolerance and quality of life. ASCO guidelines recommend a NK-1 receptor antagonist with a 5-HT3 receptor antagonist and corticosteroid for patients receiving highly emetogenic chemotherapy (HEC). Olanzapine has emerged as an alternative antiemetic, with evidence suggesting noninferiority in triple regimens. Given its favorable cost profile, we performed a pooled analysis comparing olanzapine- versus aprepitant-based triple antiemetic regimens for CINV prevention. Methods: This PRISMA-compliant review was prospectively registered in PROSPERO (CRD420261284983). Five databases were systematically searched to identify studies comparing olanzapine (OLZ) versus aprepitant (APR) based triple antiemetic regimens. The primary endpoint was complete response (CR) for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in adult patients receiving HEC. Statistical analyses were performed in R (version 2025.05.0+496; Posit). Results: 13 studies were included in the final synthesis, comprising 1,557 patients (OLZ: n = 779; APR: n = 788). CR was comparable between groups (RR 1.02, 95% CI 0.95–1.09; I² = 55.8%). Exclusion of Mehta et al. (2017) reduced heterogeneity to zero (I² = 0%). In the acute phase ( < 24 h), CR was also similar between OLZ and APR (RR 1.09, 95% CI 0.98–1.20; I² = 82.7%); however, OLZ demonstrated superior CR in the 10-mg dose subgroup (RR 1.08, 95% CI 1.03–1.14; I² = 74%). For delayed-phase CR (24-120 h), the pooled effect estimate was RR 1.11 (95% CI 0.98–1.27; I² = 84.3%). Control of nausea was significantly improved in the OLZ group compared with APR (RR 1.19, 95% CI 1.01–1.40; I² = 72.8%), particularly in anthracycline–cyclophosphamide–based regimens (RR 1.30, 95% CI 1.09–1.54; I² = 62.9%) and the 10-mg OLZ dose subgroup (RR 1.22, 95% CI 1.01–1.49; I² = 75.2%). Nausea control was also superior in both the acute phase (RR 1.13, 95% CI 1.01–1.27; I² = 76.5%) and the delayed phase (RR 1.31, 95% CI 1.05–1.65; I² = 93.3%). Control of vomiting was comparable between OLZ and APR (RR 0.99, 95% CI 0.92–1.07; I² = 0%), with no significant differences observed in the acute ( < 24 h) phase (RR 1.03, 95% CI 0.97–1.10; I² = 49%) or the delayed (24–120 h) phase (RR 1.00, 95% CI 0.97–1.04; I² = 0%). Conclusions: OLZ-based triple antiemetic regimens provide comparable CR and vomiting control to APR, with superior nausea control, particularly in anthracycline–cyclophosphamide regimens and at the 10-mg dose.

e24087 Background: Radiotherapy-induced nausea and vomiting (RINV) negatively impacts adherence and quality of life. Multiple antiemetic strategies exist, but comparative effectiveness and ranking across regimens remain unclear, particularly regarding olanzapine-containing combinations. Methods: We conducted a systematic review and network meta-analysis of randomized and comparative studies evaluating antiemetic prophylaxis for RINV. Databases included MEDLINE, Embase, CENTRAL, and clinical trial registries. Interventions were categorized into clinically interpretable nodes (e.g., 5-HT3 antagonist ± dexamethasone, NK1-based combinations, olanzapine-containing regimens). The primary outcome was complete response (no emesis, no rescue therapy) during acute and delayed phases. Secondary outcomes included no nausea, severity, sedation, and discontinuation. Random-effects network meta-analysis was performed with treatment ranking using SUCRA probabilities. Results: Twenty-two studies encompassing 3,145 patients were included. Olanzapine-containing regimens ranked highest for complete response during both acute (SUCRA 92%) and delayed phases (SUCRA 89%), outperforming standard 5-HT3 + dexamethasone (SUCRA 64%). NK1-based triple therapy showed intermediate efficacy (SUCRA 78%). Olanzapine regimens had modest increases in sedation (RR 1.14, 95% CI 1.01–1.29) but no significant differences in discontinuation rates. Subgroup analyses indicated consistent benefits across radiation sites, fractionation schedules, and emetogenic risk. Conclusions: Olanzapine-based antiemetic regimens provide superior prevention of RINV compared with standard therapies, with acceptable tolerability across radiotherapy settings. Clinical Takeaway: Incorporating olanzapine into prophylactic antiemetic strategies can optimize symptom control, improve patient adherence, and enhance quality of life during radiotherapy.