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Effects of brewing conditions on the sensory and chemical properties of Turkish black tea and their interrelationships

UFMylation orchestrates kidney development through YAP stabilization

Synergistic probiotic–chemotherapy remodeling of the intratumoral microbiome as a driver of mature tertiary lymphoid structure formation and anti-tumor immunity in colorectal cancer.

e15672 Background: Neoadjuvant chemo-immunotherapy shows promise for advanced colorectal cancer (CRC), but its efficacy is limited by immune suppression in the tumor microenvironment (TME), potentially modulated by mature tertiary lymphoid structures (mTLSs). Recent studies suggest that the intratumoral microbiome regulates tumor growth and immune function through the TME, but its contribution to mTLS formation in CRC remains unclear. We selected the composite probiotic JC-106 for its immunomodulatory effects and its reported upregulation in chemotherapy-sensitive patients. Methods: We performed multi-omics analysis on 24 non-NAC and 12 NAC CRC patients to investigate chemotherapy's impact on intratumoral microbiota and TLS formation. Using subcutaneous and orthotopic CRC models, we evaluated the anti-tumor effect of the probiotic JC-106 combined with chemotherapy. Comprehensive profiling and in vivo validation revealed the regimen's effects on metabolism and the tumor immune microenvironment. Finally, the efficacy and safety of a triple-combination therapy (JC-106, FOX, and anti-PD-1) were assessed. Results: In subcutaneous syngeneic and AOM-DSS-induced orthotopic CRC mouse models, JC-106 combined with chemotherapy reshaped the intratumoral microbiome and promoted mTLS formation. Mechanistically, the combination therapy increased the intratumoral colonization of the gut-specific symbiont Parabacteroides distasonis and promoted Th17 cell differentiation, both of which were positively correlated with TLS formation. Intratumoral injection of Parabacteroides distasonis enhanced Th17 cell proportions in a linoleic acid depletion-dependent manner, thereby initiating mTLS development. Clinically, JC-106 alleviates chemotherapy-induced PD-1 upregulation to suppress immune escape, and synergizes with chemotherapy to improve immunotherapy efficacy. Conclusions: Our findings support the potential of composite probiotics as a promising strategy to enhance TLS-dependent neoadjuvant chemo-immunotherapy in CRC.

Genomic instability score (GIS) and real-world outcomes in patients (pts) with advanced ovarian cancer (aOC) using a U.S. health database.

e17565 Background: Identification of homologous recombination deficiency biomarkers are needed to determine which pts with aOC will most likely derive benefit from poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment (tx). Studies of various GIS cutoffs have shown an association with improved outcomes (current standard cutoff, ≥42). Real-world data is needed to explore associations between GIS cutoffs and real-world outcomes. We evaluated the association of GIS with real-world progression-free survival (rwPFS) and time to next tx (TTNT) in pts with aOC treated with PARPi as first-line maintenance (1LM). Methods: The Flatiron Health database was used to retrospectively evaluate eligible adults with aOC who received 1L platinum-based chemotherapy followed by 1LM PARPi between 01Jan2017 and 31Mar2025. Pts were followed from index (start of 1LM PARPi) to earliest of death, loss to follow-up, or study end. Associations between GIS cutoffs (≥33/<33, ≥42/<42, ≥60/<60, GIS-low/medium/high, and unadjusted thresholds for every cutoff from 25 to 70) and rwPFS (time from index to disease progression or death) or TTNT (time from index to start of any second-line tx or death) were estimated per Kaplan Meier and Cox regression (unadjusted and adjusted for demographic and clinical characteristics) analyses. Results: The analysis included 121 pts; most had serous histology (84%), had BRCA wild-type aOC (83%), and received care in a community setting (82%). For each GIS cutoff, pts with a higher GIS had a longer median rwPFS and TTNT (Table). In unadjusted threshold analyses of cutoffs from 25 to 70, every cutoff from 26 to 63 was associated with significant clinical benefit for both rwPFS and TTNT, with the strongest magnitude of association at GIS 41/42 for rwPFS and 42 for TTNT. As only 44% of pts had progression data, adjusted Cox regression for rwPFS was not performed. In adjusted Cox models for TTNT, pts with higher vs lower GIS for each cutoff had a longer TTNT (Table); the strongest association was at GIS cutoff 42. Conclusions: Higher GIS at any cutoff was associated with improved rwPFS and TTNT in pts treated with a 1LM PARPi. GIS cutoff ≥33 showed clinical benefit, with GIS cutoff ≥42 showing the greatest magnitude of rwPFS and TTNT benefit across analyses. GIS cutoff: <33 a ≥33 <42 a ≥42 <60 a ≥60 rwPFS n 23 30 26 27 36 17 Median (95% CI), mo 9.4 (4.2–11.3) 26.1 (11.6–NE) 10.3 (5.6–11.5) 30.4 (13.2–NE) 11.3 (9.4–13.8) NE (10.0–NE) Unadjusted HR (95% CI) 0.25 (0.12–0.53) b 0.21 (0.10–0.47) c 0.36 (0.15–0.88) d TTNT n 64 57 76 45 93 28 Median (95% CI), mo 11.0 (8.2–14.2) 26.2 (12.3–NE) 10.7 (8.2–12.9) NE (21.9–NE) 12.2 (9.9–14.7) NE (17.7–NE) Unadjusted HR (95% CI) 0.43 (0.26–0.71) e 0.26 (0.14–0.47) c 0.36 (0.18–0.72) e Adjusted HR (95% CI) 0.46 (0.26–0.79) e 0.22 (0.11–0.43) c 0.32 (0.15–0.70) e a Ref for HR comparison. b P ≤ 0.001; c P ≤ 0.0001; d P ≤ 0.05; e P ≤ 0.01. HR, hazard ratio; NE, not estimable.

Trial characteristics and results reporting among oncology clinical trials involving African countries.

1589 Background: Sub-Saharan Africa (SSA) faced ~801,000 new cancer cases and ~520,000 cancer deaths in 2020, with deaths projected to reach 1 million annually by 2030. African trial activity remains scarce (<1% of global trials), with sparse reporting. We measured results reporting for oncology trials involving African sites and identified trial characteristics associated with results disclosure. Methods: Using ClinicalTrials.gov, we identified 1,140 completed oncology trials (1992-2023) involving ≥1 African site. We classified trials by country, institution, region, and funder, reporting proportions, ORs (95% CI), and multivariable logistic regression. Results: Among 1,140 trials across 38 countries, most were single-country (93.7%), single-institution (76.7%), and North Africa only (58.2%). Most were non-industry-sponsored (68.8%), interventional (79.5%) and randomized (61.1%). Enrollment was ≤100 participants in 666 trials (58.4%). Overall, 25.2% posted results. Multi-country trials reported more than single-country (59.7% vs 22.8%); multi-institution exceeded single-institution (60.5% vs 14.4%). SSA-only (48.0%) and both-region trials (72.1%) exceeded North-Africa-only (7.2%). Industry-funded reported more than non-industry (70.5% vs 4.6%). Phase III exceeded other phases (64.0% vs 10.6%). In multivariable analysis, industry sponsorship, multi-institution and multi-country configuration, SSA region, and phase 3 status were independently associated with results posting (Table 1). Conclusions: Nearly three-quarters of completed oncology trials conducted in Africa have not publicly reported results, highlighting substantial research waste and a critical ethical failure to translate participant contributions into accessible evidence. This analysis identifies independent, actionable determinants of reporting transparency. Strengthening African clinical trial infrastructure and coupling reporting requirements with systematic monitoring and accountability are essential to improve evidence generation and promote equity as the continent’s cancer burden continues to rise. Multivariable predictors of results reporting. Predictor Adjusted OR (95% CI) p-value Industry funding (ref: non-industry) 28.40 (19.1-42.2) 0.001 Multi-institution (ref: single) 5.81 (4.08-8.26) 0.001 Multi-country (ref: single) 2.12 (1.18-3.81) 0.012 Sub-Saharan only (ref: North Africa) 6.82 (4.68-9.94) 0.001 Both regions (ref: North Africa) 8.46 (3.45-20.7) 0.001 Phase 3 (ref: other/NA) 3.24 (2.26-4.64) 0.001 Interventional (ref: observational) 4.12 (1.48-11.5) 0.007 Enrollment >100 (ref: ≤100) 1.89 (1.32-2.71) 0.001

Trajectories of cervical cancer patients through the health systems of Colombia and Guatemala

e13800 Cervical cancer (CC) is the 2nd most prevalent cancer among women from low and middle-income countries. Latin America faces the 2nd highest mortality globally, but substantial differences are observed between countries. Colombia (COL) and Guatemala (GTM) are upper-middle income countries; however, they significantly differ in CC mortality. We analyzed trajectories of CC patients in retrospective cohorts from GTM and COL. Patients 18 years and older, newly diagnosed with locally advanced CC were included from June 2023 to January 2019. Patients were enlisted in referral centers from different healthcare subsystems in every country. A comparison was done on patterns of care, time to care, resource use, trajectory clusters, and mortality. Overall, 201 and 237 patients from GTM and COL were included, respectively. Mean age was 51.2. Education and public coverage were lower in GTM, whereas indigenous origin and rural housing were lower in COL. Median follow-up was 29.2 and 21.6 months in GTM and COL. COL patients showed lower chemotherapy compliance, and lower administration of IMRT and brachytherapy was observed in GMT. Mortality was higher in GTM over COL (8.4 and 5.7 per 1,000 women-months; respectively). The multivariate analysis only showed disease relapse, and the use of extended-field radiotherapy without IMRT significantly associated with higher mortality (OR 14.8 95%CI 7.42-31.01 and 2.2 95%CI 1.09-4.58). On the contrary, the use of brachytherapy was significantly associated with lower mortality (OR 0.34 95%CI 0.15-0.80). In total 9 trajectories of care were identified in GTM and 26 in COL. Despite differences in social determinants, trajectories of care, and treatment compliance; a lower access to standard treatment was observed as the major contributing factor to higher mortality. A need to focus on treatment effectiveness is highlighted as an objective mean to evaluate quality of care. Treatment pattern Guatemala Colombia p value Concomitant chemoradiation (%) 98.6 94.1 0.03 Type of external beam radiotherapy (%)IMRTExtended field 23.460.6 100.051.0 <0.01 0.08 Brachytherapy (%) 81.5 95.3 <0.01 Treatment compliance (%) 74.4 78.5 0.31 Supportive care (%) 4.3 56.1 <0.01 Time to treatment Time from diagnosis to treatment (median months) 1.9 2.9 <0.01 Time to treatment completion (median months) 2.1 2.4 <0.01

Palliative care involvement at the end of life in advanced cancer.

12033 Background: High-intensity end-of-life (EoL) care in advanced cancer is common, costly, and often misaligned with patient goals, despite limited survival benefits. Value-based oncology emphasizes high-quality, goal-concordant care while reducing non-beneficial interventions. Palliative care is central to this model, yet its impact on overall spending versus patterns of care intensity near death remains unclear. We evaluated whether palliative care involvement in the final 30 days of life was associated with differences in total expenditures and healthcare resource allocation in patients with advanced cancer. Methods: We conducted a retrospective cohort study of adults with advanced cancer who died within an integrated health system between 2022 and 2025. Palliative care exposure was defined as ≥1 palliative encounter within 30 days of death. Financial data were obtained from enterprise cost-accounting systems; clinical and utilization data were derived from the electronic health record and institutional cancer registry. Outcomes included total 30-day healthcare charges and proportional spending across major service categories reflecting care intensity. Median charges were compared using Wilcoxon rank-sum tests, and spending distributions were analyzed via chi-square tests. Results: Among 1,635 decedents, 195 received palliative care within 30 days of death, a period associated with the highest concentration of EoL healthcare use. Median total 30-day charges did not differ significantly between patients who received palliative care and those who did not ($14,610 vs $17,100; p = 0.054). However, palliative care involvement was associated with a significant shift in spending patterns. Compared with patients without palliative care, those receiving palliative care had a lower proportion of spending on inpatient, procedural, diagnostic, and therapeutic services and a higher proportion on pharmacy, invasive therapeutic, home health, and hospice services. Overall spending distribution differed significantly between groups (p = 0.046). Across the cohort, inpatient and observation services accounted for the largest share of expenditures, followed by pharmacy, procedural, and invasive therapeutic services, with hospice representing a minority of total spending. Conclusions: EoL palliative care involvement was not associated with significant reductions in total healthcare spending but was linked to differences in care intensity, reflected by a redistribution of expenditures from inpatient and procedural services to pharmacy, invasive therapeutic, and home health care. The value of palliative care in oncology lies not in cost savings but in promoting high-quality EoL care that aligns with patient goals and oncology care priorities. Future analyses will include patient-reported outcomes to examine how shifts in care intensity and spending relate to EoL symptom burden, quality of life, and goal-concordant care.

Real-world outcomes of TP53-mutated acute myeloid leukemia at a single institution.

e18543 Background: TP53-mutated acute myeloid leukemia (AML) represents a high-risk subset with poor response to conventional intensive chemotherapy. Hypomethylating agents with or without venetoclax (VEN/HMA) have emerged as a major treatment option for TP53-mutated AML. This study reports real-world clinical outcomes of TP53-mutated AML at a single institution. Methods: We conducted a retrospective cohort study of adult patients with TP53-mutated AML treated at Stony Brook University Hospital between 2020 and 2025. Demographics, disease characteristics, treatments and outcomes were collected. Endpoints included time to treatment initiation (TTI) and overall survival (OS). Median follow-up was calculated using the reverse Kaplan-Meier method from date of initial biopsy to date of expiration. Results: Nineteen patients were identified; median age at diagnosis was 80 years (range 49-91). Secondary AML was present in 42% (n=7) including preceding myelodysplastic syndrome (n=5) or therapy-related AML (n=2). TP53 biallelic mutations or loss was present in 37% (n=7) and complex karyotype in 89% (n=17). Thirteen patients (68%) received therapy; median TTI was 10 days (range 5-99). First-line therapy included Venetoclax-based regimens (n=10), 7+3 intensive chemotherapy (n=1), single-agent azacitidine (n=1) and CPX-351 (n=1). Three patients treated with venetoclax-based therapy received subsequent lines of therapy upon progression. One patient ultimately underwent haploidentical allogeneic stem cell transplant with OS of 456 days. Median follow-up and median OS were both 79 days (range 6-456); all 19 patients died. Among patients receiving lower intensity therapy (n=11, including 10 venetoclax-based), median OS was 112 days, compared to 27 days in untreated patients (p=0.00108). Thirty-day mortality was lower in treated versus untreated patients (8% vs. 67%), with a larger difference at 60 days (23% vs. 83%). There was no significant difference in age or Eastern Cooperative Oncology Group (ECOG) performance status between treated and untreated patients. Among the six untreated patients, five presented with neutropenic fever and opportunistic infections, required Medical Intensive Care Unit admission, and rapidly declined while hospitalized. The remaining untreated patient could not receive transfusions due to religious beliefs. Conclusions: In this real-world limited cohort of TP53-mutated AML, outcomes remain dismal. Approximately one-third of patients did not receive AML-directed therapy due to neutropenic fever and rapid clinical decline, or inability to receive supportive care. While therapy was associated with prolonged OS, the apparent survival advantage is likely confounded by baseline disease severity rather than treatment alone. Even among treated patients, survival remained limited, and durable disease control was rare, reinforcing TP53-mutated AML as a critical area of unmet need.

Combination of golidocitinib (a JAK1 inhibitor) with anti–PD-1 antibody to improve tumor response and patient quality of life: Preliminary results from an ongoing JACKPOT 33 study.

8555 Background: Chemo-immunotherapy remains the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver mutations. Unfortunately, treatment resistance is inevitable. Janus kinase (JAK) inhibition may improve the efficacy of immunotherapy by pivoting T cell exhaustion dynamics, enhancing and extending patient response. Herein, we report the anti-tumor efficacy and safety data from an ongoing phase 2 study (NCT06198907, JACKPOT33) evaluating golidocitinib, a JAK1-specific inhibitor, combined with sintilimab, an anti-PD-1 antibody, as first-line treatment in patients with PD-L1 positive advanced NSCLC without driver mutations. Methods: Eligible patients with advanced NSCLC with PD-L1 TPS ≥ 1% were enrolled in the study. Patients received two cycles of chemo-immunotherapy only, followed by golidocitinib 150 mg orally once daily plus sintilimab 200 mg intravenous every 3 weeks until disease progression, intolerance, up to 2 years of treatment, or other discontinuation criteria were met. The primary objective was to evaluate the anti-tumor efficacy, and the secondary objectives included safety and tolerability. Results: As of December 23, 2025, a total of 47 patients were enrolled in the JACKPOT33 study. The median age of these patients was 63 years, with 87.2% males, 61.7% with non-squamous histology, 40.4% with PD-L1 high (TPS ≥50%) and 59.6% with PD-L1 low (TPS 1-49%) expression. Most (74.5%) of the patients had metastatic disease at baseline, with 8.5% having brain metastasis. Per investigator assessment, the overall response rate (ORR) after two cycles of chemo-immunotherapy was 42.6%. Following the addition of golidocitinib with sintilimab, deeper tumor shrinkage and additional responders were observed, resulting in an ORR of 63.8% (30/47). The improvement in ORR with golidocitinib was most profound in patients with high PD-L1 levels, with rates of 84.2% vs. 50% in the high and low expression cohorts, respectively. No difference in ORR was observed between patients with squamous or non-squamous carcinoma (61.1% vs 65.5%). As of the data cut-off date, 32 out of 47 patients remained on treatment and benefiting. The longest treatment duration reached 15.9 months. The combination of golidocitinib and sintilimab was well tolerated. The incidence of immune-related adverse effects was markedly decreased, and patients' self-reported quality of life significantly improved. No new safety signal was observed. Conclusions: In treatment-naïve patients with advanced NSCLC, golidocitinib plus sintilimab following chemo-immunotherapy demonstrated encouraging and durable anti-tumor efficacy, particularly in those with high PD-L1 expression. A profound decrease in immune-related adverse effects was observed. Updated data will be presented at the conference. Clinical trial information: NCT06198907 .

Estimating survival in advanced cancer: A prospective single-center study on the accuracy of oncologists’ prognostic accuracy (Pre-Sur).

11133 Background: The ability to estimate survival is a cornerstone of care for patients (pts) with advanced cancer, influencing therapeutic strategies, access to clinical trials, and timing of palliative care referral. Existing evidence on clinical prediction of survival (CPS) largely derives from end-of-life pts. The Pre-Sur study addresses this gap by evaluating oncologists’ prognostic accuracy in pts with metastatic solid tumors starting first-line therapy and investigating discordance-related factors. Methods: Pre-Sur is a prospective, observational, monocentric study enrolling pts with advanced tumors prior to first-line therapy (hormonal therapy was excluded). During the baseline consultation, clinicians provided an estimated survival timeframe using categorical intervals (0-4 to >36 months). The primary endpoint was concordance between CPS and overall survival (OS). Survival estimates and outcomes were analyzed descriptively and through cross-tabulation. Secondary analyses explored factors potentially influencing accuracy, including ECOG-PS, age, comorbidities, and clinician characteristics, using Chi-square tests and multivariable models. Results: From October 2022 to December 2025, 183 pts were enrolled; 135 completed the required follow-up. 58% of pts were male and 49% were ≥75 years. Gastrointestinal (45%) and thoracic (35%) cancers were the most prevalent. Median CPS (mCPS) was 18.0 months (95%CI: 15.9–20.0), median OS (mOS) of 8.0 months (95%CI: 5.9–10.0). Prognostic estimates were accurate in 17% of cases, optimistic in two-thirds, and underestimated in less than one-quarter. No significant associations emerged for sex, tumor site, PS or target therapy use. mCPS were often more consistent with the mOS reported in randomized clinical trials (RCT); the observed real-world OS were inferior to that expected from RCT (Table 1). Conclusions: This study highlights the difficulty of predicting OS in pts with metastatic solid tumors. CPS may be influenced by expectations derived from RCT outcomes, which may not fully capture the complexity of real-world pts. Prognostic evaluation in clinical practice should integrate features such as age, PS, comorbidities, and disease burden, to improve prognostic accuracy and support informed decision-making. Overall survival and clinical prediction of survival by disease sites. Site Patients, n (%) mOS, months (CI 95%) mCPS, months (CI 95%) mOS trend in registrative RCTs, months Lung 44 (32.2) 7 (2-12) 12 (11-13) 12-26 Colorectal 24 (17.8) 9 (5-13) 18 (13-23) 25-30 Pancreas 15 (11.1) 8 (2-14) 24 (21-27) 11 Gastric 11 (8.1) 5 (2-8) 12 (7-17) 14 Head and neck 6 (4.4) 6 (0-13) 30 (NA-NA) 15 Kidney 6 (4.4) 6 (4-8) 18 (5-30) 45 Biliary ducts 5 (3.7) 2 (1-3) 18 (13-23) 12 Pleural 4 (3.0) 2 (NA-NA) 8 (NA-NA) 12 Skin 4 (3.0) 22 (NA-NA) 12 (NA-NA) 33 Bladder 3 (2.2) 11 (0-27) 18 (8-28) 21

Using organoids to predict efficacy of adjuvant treatment to improve outcome in resectable pancreatic cancer: UNITEPANC (AIO-PAK-0424), a prospective, multicenter, proof-of-concept trial of the AIO Pancreatic Cancer Group.

TPS4266 Background: Pancreatic cancer (PDAC) is a heterogeneous disease and there is a lack of predictive biomarker to guide treatment. Patient tumor derived organoids (PDO) recapitulate key morphological and genetic features and may preserve patient-specific drug response phenotypes Methods: UNITEPANC is a prospective, proof of concept, multicenter IIT of the German AIO PDAC Group and funded by the German Cancer Aid. UNITEPANC examines the feasibility of an organoid-educated adjuvant treatment approach with respect to organoid establishment, expansion and characterization and its potential role for selecting an optimal adjuvant treatment in PDAC in a multicenter setting. Preparatory activities like harmonizing SOPs and round-robin-tests for generation of organoids and organoid-based pharmacotyping in the trial centers and the different Organoid Facilities have been completed and evaluated. UNITEPANC examines selection of adjuvant chemotherapy by pharmacotyping of tumor organoids. Options for adjuvant treatment are gemcitabine, gemcitabine/capecitabine, gemcitabine/nab-paclitaxel or mFOLFIRINOX. Major inclusion criteria are R0 or R1 resected, histologically confirmed PDAC and patients in principle, suitable for mFOLFIRINOX treatment in the adjuvant setting, postoperative Ca19-9 < 180 U/ml, and a timely PDO-based chemotherapy recommendation by the UNITEPANC Organoid Board to guarantee a start of the adjuvant treatment within 12 weeks after resection. UNITEPANC is an interventional, prospective, multicenter, single-arm trial. 92 patients shall be allocated to the trial for the generation of organoids, 38 patients shall be enrolled for PDO-based adjuvant treatment and 34 patients need to be analyzed as ITT population in the follow-up period. Efficacy: The efficacy endpoint of the trial is purely descriptive and intended to obtain a signal for further development of the strategy. This requires the proof of an efficient 1) generation and 2) expansion of PDO and 3) a clear sign that an organoid-educated treatment selection is superior to standard treatment with mFOLFIRINOX. For 1) and 2) we have chosen a rate of 75% and 60%, respectively, according to the literature. For 3): The approach would be considered promising, if the true 18-months-DFS rate is 77% (corresponding to a hazard ratio of 0.5 compared to Prodige-24, 80% power, one-sided type I error 0.1. HR-QoL data will be analyzed (QLQ-C30, Pan26). Additionally, an extensive translational program is enclosed. UNITEPANC has started recruitment in Q3/2025. Clinical trial information: 2023-510490-34-00.

Randomized phase II trial of olaparib and pembrolizumab vs olaparib alone as maintenance therapy in metastatic pancreatic cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2) mutations: SWOG S2001.

4012 Background: Preclinical studies have demonstrated that PARP inhibitors modulate the immune microenvironment by increasing genomic instability, PD-L1 expression and activating the immune inflammatory stimulator of interferon genes (STING) pathway. The POLAR trial demonstrated promising results combining pembrolizumab with olaparib as maintenance therapy in patients (pts) with homologous recombination deficiency (HRD) mutations. S2001 is a randomized phase II trial evaluating the addition of pembrolizumab to olaparib as maintenance therapy in patients with gBRCA1/2. Methods: Eligible pts had mPDA with gBRCA1/2 mutations and had received a minimum of 4 months of platinum-based chemotherapy without progression. Pts were randomized 1:1 to olaparib 300 mg twice per day plus pembrolizumab 200 mg every 3 weeks or olaparib alone. The primary endpoint was progression-free survival (PFS) with a target hazard ratio (HR) of 0.6 (median PFS 7.0 vs 11.7 months) with 1-sided alpha=0.1 and 80% power. Secondary outcomes were safety and tolerability, overall survival (OS), overall response rate (ORR), and disease control rate (DCR). The accrual goal was 88 pts to have 78 eligible for analysis. Differences in PFS by treatment arm were assessed via stratified log-rank test, with first line platinum-based chemotherapy, Zubrod PS, and disease status after first line treatment as stratification factors. Tissue and blood samples for correlative studies were banked. Results: The study enrolled 73 patients, with 68 eligible, and was closed for futility after a planned interim analysis showed that PFS was not improved in the pembrolizumab + olaparib arm (p=0.82), despite higher ORR (p=0.20) (Table). Treatment was well tolerated, with no grade 4-5 treatment-related adverse events and similar toxicity profiles across arms. Autoimmune toxicities on the experimental arm included adrenal insufficiency, hyperthyroidism, and hypothyroidism. Grade 3 adverse events in both arms included neutropenia, anemia, thrombocytopenia, gastrointestinal toxicity and fatigue. Conclusions: S2001 is the first randomized controlled trial evaluating the addition of pembrolizumab to olaparib in pancreas cancer. Despite doubling the ORR and improvement in DCR and PFS in the experimental arm, the high bar of improving PFS to 11.7 months was not met. Activity seen in the experimental arm of S2001 is comparable to the HRD cohort of the POLAR trial which demonstrated ORR 35%, DCR 90% and PFS of 8.2 months. Further follow-up for mature survival outcomes and translational analysis of DNA and RNA are planned. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819 with additional support from by Merck & Co, Inc. Clinical trial information: NCT04548752 . Pembrolizumab + Olaparib (n=34) Olaparib (n=34) Median PFS 8.2 months 6.4 months Median OS 20.0 months 22.1 months ORR 28.1% 14.3% DCR 84.4% 64.3%

Trends and disparities in diabetes-associated cancer mortality in the United States, 1999–2020.

11190 Background: Diabetes mellitus (DM) is increasingly recognized as an important contributor to cancer mortality, yet long-term population-level trends and sociodemographic disparities in diabetes-associated cancer deaths in the United States remain insufficiently characterized. Methods: We analyzed U.S. Multiple Cause of Death data from the CDC WONDER database for 1999–2020. Deaths with neoplasia as the underlying cause of death and diabetes mellitus listed as a contributing cause were included. Annual deaths and crude mortality rates were examined across year, Census region, state, 2013 urbanization level, 10-year age groups, sex, race, and Hispanic origin. Temporal trends were quantified using average annual percent change (AAPC) derived from log-linear regression models over the 1999–2020 period. Results: From 1999–2020, diabetes-related neoplasia deaths totaled 588,693 (mean 26,759/year), with annual deaths rising 77.9% (20,427 in 1999 to 36,343 in 2020) and crude mortality increasing 50.7% (7.3 to 11.0 per 100,000), corresponding to an overall AAPC +1.24%/year. By sex, trends increased faster in males (AAPC +1.75%) than females (AAPC +0.55%). By Census region, AAPC was highest in the West (+2.00%) and South (+1.98%), followed by the Midwest (+0.65%), while the Northeast declined (−0.30%). By 2013 urbanization, the steepest rises occurred in Noncore nonmetro (+2.43%) and Micropolitan nonmetro (+1.61%), exceeding Medium metro (+1.54%), Small metro (+1.22%), Large central metro (+0.97%), and Large fringe metro (+0.80%). By race, AAPC was highest for American Indian/Alaska Native (+2.38%) and Asian/Pacific Islander (+2.30%), followed by White (+1.45%) and Black (+0.30%). By Hispanic origin, AAPC was higher in Hispanic/Latino (+2.42%) than Not Hispanic/Latino (+1.33%) (Not stated: insufficient rate series for AAPC). By age, increases were greatest at 35–44 years (+1.45%) and 25–34 years (+1.18%), with smaller increases at 45–54 (+0.62%) and ≥85 (+0.62%), while older mid-life groups declined (65–74: −0.61%, 55–64: −0.27%, 75–84: −0.04%). State-level AAPC ranged from Kentucky (+6.55%), Arizona (+5.07%), Oklahoma (+4.81%), Colorado (+4.66%), and Arkansas (+4.61%) to District of Columbia (−3.44%), Connecticut (−2.91%), Massachusetts (−1.88%), Illinois (−1.38%), and Delaware (−1.24%). Conclusions: Diabetes-associated cancer mortality increased substantially in the United States from 1999–2020, with widening disparities by geography, urbanization, race/ethnicity, sex, and age. The disproportionate rise in rural areas, younger adults, and select racial and ethnic groups underscores the need for integrated cancer–diabetes prevention strategies and targeted public health interventions to mitigate future mortality burden.

Individualizing first-line treatment choices in metastatic urothelial carcinoma (mUC): Results from a cross-sectional study of physicians in Europe.

e16579 Background: The expanding first-line (1L) treatment options for mUC have introduced complexity to therapy selection. While recommended treatments offer clinical benefits, their toxicity profiles can limit routine use, and evidence on how physicians make prescribing decisions is limited. We aimed to understand physicians’ decision-making for 1L mUC treatment choice based on hypothetical patient (pt) profiles. Methods: Data were drawn from the Adelphi Real World mUC Disease Specific Programme, a cross-sectional survey of medical oncologists/urologists and their pts with mUC in France, Germany, Italy, Spain, and the UK between Dec 2023 and Jul 2024. Physicians were asked to consider a list of pt types and select which of the 4 1L treatment options they would be most likely to prescribe for the majority of their pts with these profiles. Treatment options included platinum-based chemotherapy followed by avelumab 1L maintenance (PBC + Ave 1LM), enfortumab vedotin + pembrolizumab (EV + P), cisplatin/gemcitabine + nivolumab (Cis/Gem + Nivo), and other. All analyses were descriptive. Results: Of 238 physicians surveyed, 149 (63%) worked in academic practices, 60 (25%) in community-based practices, and 29 (12%) in other care settings. At data collection, physicians were responsible for treatment decisions for a median (IQR) of 23 (8-20) pts. Over 50% of physicians reported that they would prescribe PBC + Ave 1LM for pts with liver disease (53%) or those who are cisplatin-eligible (52%). For pts with high body mass index (BMI), or pts with low or high tumor burden, most physicians reported that they would prescribe PBC + Ave 1LM (47%, 45% and 47%, respectively). Overall, 45% of physicians stated that they would prescribe EV + P for pts with preexisting peripheral neuropathy. For frail/older pts, 34% of physicians would choose EV + P and 26% would choose PBC + Ave 1LM (Table). Conclusions: This real-world study provides contemporary insights into mUC treatment choice among practicing European physicians in an evolving therapeutic landscape. Physicians’ choice of 1L treatment was highly dependent on pt profile, demonstrating the importance of using a multifactorial decision-making strategy. Evidence-driven eligibility criteria and adherence to guidelines are crucial to inform clinical decision-making in a personalized healthcare model. Physician-reported 1L treatment choice (N=238). Pt profile, n (%) PBC + Ave 1LM EV + P Cis/Gem + Nivo Other Liver disease 126 (53) 72 (30) 11 (5) 29 (12) Frail/older 62 (26) 81 (34) 14 (6) 81 (34) High BMI 112 (47) 88 (37) 17 (7) 21 (9) Low tumor burden 108 (45) 91 (38) 24 (10) 15 (6) High tumor burden 111 (47) 90 (38) 31 (13) 6 (3) Preexisting peripheral neuropathy 76 (32) 106 (45) 15 (6) 41 (17) Only lymph node involvement 115 (48) 87 (37) 26 (11) 10 (4) Liver metastases 113 (47) 85 (36) 29 (12) 11 (5) Cisplatin-eligible 124 (52) 71 (30) 37 (16) 6 (3)

Failure-to-rescue following major surgical complications in gynecologic oncology: A National Inpatient analysis.

e23124 Background: Postoperative complications are common after major gynecologic oncology surgery, yet mortality is not inevitable. Failure-to-rescue (FTR), defined as death after a treatable complication, reflects hospital capacity to recognize and manage deterioration, but national benchmarks in gynecologic oncology are limited. Methods: We performed a retrospective, survey-weighted analysis of the U.S. National Inpatient Sample (NIS), 2016 to 2023. Adult hospitalizations (age 18 years or older) with gynecologic malignancy (ICD-10-CM C51 to C58) undergoing major gynecologic surgery (ICD-10-PCS female reproductive system procedures) were included. Encounters with palliative care coding (Z51.5) were excluded. Major postoperative complications were identified using ICD-10 diagnosis and procedure codes and included sepsis or septic shock, hemorrhage or transfusion-requiring bleeding, venous thromboembolism, acute kidney injury, and bowel injury or peritonitis. The primary outcome was FTR, defined as in-hospital death among admissions with one or more major complications. Secondary outcomes included overall mortality, ICU escalation proxy (mechanical ventilation or shock), length of stay (LOS), cost, and discharge disposition. Results: Among 65,669 gynecologic oncology surgical admissions, 33.27% experienced one or more major postoperative complications (95% CI 32.77 to 33.77). The most frequent complications were bleeding (25.38%, 95% CI 24.89 to 25.88) and acute kidney injury (9.53%, 95% CI 9.27 to 9.78). Overall in-hospital mortality was 0.36% (95% CI 0.32 to 0.41). Among complication cases, mortality was 1.01% (95% CI 0.88 to 1.16), representing the FTR rate in the complication subgroup. ICU escalation among complication cases occurred in 5.68% (95% CI 5.36 to 5.99), including mechanical ventilation in 3.01% (95% CI 2.78 to 3.25) and shock in 3.33% (95% CI 3.08 to 3.57). Complications were associated with higher resource use, with mean LOS 7.47 days versus 3.14 days without complications, and mean cost $34,746.72 (95% CI $33,613.31 to $35,880.14) versus $20,442.15 (95% CI $19,836.75 to $21,047.55). Complications were also associated with higher rates of non-home discharge. Conclusions: In a national sample of gynecologic oncology surgery hospitalizations, one-third experienced major postoperative complications, while mortality among complication cases was approximately 1%. Complications were associated with substantially higher ICU escalation, LOS, cost, and non-home discharge. These findings provide national benchmarks for complication burden and failure-to-rescue in gynecologic oncology and support FTR as a practical quality metric for surgical oncology improvement efforts.

Retrospective study on safety and efficacy of hypofractionated versus conventional fractionated sequential radiotherapy for stage III unresectable non-small cell lung cancer.

e20058 Background: Large-scale clinical data directly comparing hypofractionated radiotherapy (HypoRT) with conventional fractionated radiotherapy (ConvRT) in the sequential setting for stage III unresectable non-small cell lung cancer (NSCLC) are lacking. This study aimed to evaluate whether a 4-week HypoRT regimen is as effective and safe as a 6-week ConvRT regimen. Methods: Large-scale clinical data directly comparing hypofractionated radiotherapy (HypoRT) with conventional fractionated radiotherapy (ConvRT) in the sequential setting for stage III unresectable non-small cell lung cancer (NSCLC) are lacking. This study aimed to evaluate whether a 4-week HypoRT regimen is as effective and safe as a 6-week ConvRT regimen. Results: From October 2018 to December 2024, 280 patients were included and allocated in a 2:1 ratio to the HypoRT group (n = 178) or the ConvRT group (n = 102). Baseline characteristics were balanced. With a median follow-up of 47.2 months, HypoRT did not meet the pre-specified non-inferiority margin for OS compared to ConvRT. Median OS was 51.4 months in the HypoRT group and 44.6 months in the ConvRT group (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 0.78–1.36). The 1-, 2-, 3-, and 5-year OS rates were 90.3%, 72.8%, 58.4%, and 46.5% for HypoRT, and 89.1%, 71.2%, 57.4%, and 45.8% for ConvRT, respectively. Median PFS was similar between groups (19.5 vs. 16.2 months; HR = 1.11; 95% CI, 0.82–1.35; p = 0.68). Regarding safety, the HypoRT group had a significantly higher incidence of grade ≥2 radiation esophagitis (67.6% vs. 22.5%; p < 0.001). No significant differences were observed in the incidence of grade ≥2 radiation pneumonitis (16.5% vs. 18.7%; p > 0.05), grade ≥3 acute hematological toxicity (59.8% vs. 66.5%; p > 0.05), or long-term toxicity profiles. Conclusions: In this retrospective analysis, the 4-week HypoRT regimen (60 Gy/20 F) did not demonstrate statistical non-inferiority in OS compared to the 6.5-week ConvRT regimen (66 Gy/33 F) for stage III unresectable NSCLC treated with sequential chemoradiotherapy. While survival outcomes were numerically similar, HypoRT was associated with a significantly increased risk of grade ≥2 esophagitis. These findings highlight the need for careful patient selection and toxicity management when considering hypofractionated schedules in this setting.

Association of omentectomy with reduced therapeutic efficacy of lenvatinib plus pembrolizumab in patients with endometrial cancer.

e17613 Background: Recently, omentum has been suggested to be immunologically active. Therefore, we investigated the effect of prior omentectomy on the efficacy of lenvatinib + pembrolizumab (LP) therapy in patients with endometrial cancer (EC). Methods: This retrospective study included 95 patients with recurrent EC treated with LP between December 2021 and March 2025 at our institutions. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Multivariable Cox regression analyses included factors such as omentectomy status, MMR status, FIGO stage (I/II or III/IV), histology (endometrioid or others), platinum-free interval (PFI) (<6 or ≥6 months) and the number of prior regimens (1 or ≥2). Results: Overall, 95 patients were enrolled in the study (omentectomy group, 50; no-omentectomy group, 45). Moreover, six patients in the no-omentectomy group, did not undergo primary surgery and predominantly presented with stage IV disease. Molecular profiling was used to identify 9 dMMR and 86 pMMR tumors. Advanced stage (III/IV), endometrioid histology, PFI <6 month, and ≥2 prior regimens were observed in 64%, 42%, 64%, and 30% of the patients in the omentectomy group and 58%, 60%, 60%, and 31% of the patients in the no-omentectomy group. Patients in the no-omentectomy had a significantly longer median PFS (15.4 vs. 8.2 months; p = 0.001) and OS (34.9 vs. 21.7 months; p = 0.090). Multivariable analysis revealed that omentectomy was independently associated with shorter PFS (HR 2.18; 95% CI, 1.23–3.88; p = 0.008), but was not an independent predictor of OS (HR 1.11; 95% CI 0.58–2.12; p = 0.750) [Table]. Histology-specific analyses of the major subtypes, including endometrioid carcinoma ( n = 48), serous carcinoma ( n = 20), and carcinosarcoma ( n = 18), revealed that omentectomy was associated with more favorable outcomes only in patients with serous carcinoma. Therefore, further analysis, excluding patients with serous carcinoma, was performed. In this non-serous cohort, multivariable Cox regression analyses demonstrated that omentectomy remained independently associated with shorter PFS (HR 3.29; 95% CI, 1.69–6.41; p < 0.001) and had a trend toward shorter OS (HR 1.99; 95% CI, 0.93–4.26; p = 0.076). Conclusions: Patients without prior omentectomy had better outcomes following LP therapy. Thus, omentum may contribute to antitumor immune regulation. 　 Progression-free survival Overall survival Variables 　 HR 95% CI p -value HR 95% CI p -value Omentectomy status OMTx vs No-OMTx 2.18 1.23–3.88 0.008 　 1.11 0.58–2.12 0.750 MMR status dMMR vs pMMR 0.36 0.13–1.00 0.051 0.19 0.04–0.87 0.032 FIGO stage III/IV vs I/II 1.00 0.58–1.75 0.992 1.48 0.74–2.98 0.272 Histology non-endometrioid vs endometrioid 1.09 0.63–1.88 0.768 2.47 1.22–5.00 0.012 PFI ≥6 vs <6 months 0.47 0.26–0.85 0.012 0.34 0.15–0.77 0.009 Number of prior regimens ≥2 vs 1 0.91 0.51–1.61 0.744 1.03 0.52–2.05 0.937

Inpatient chemotherapy in lung cancer: Survival outcomes in small cell and non–small cell lung cancer.

e20592 Background: Patients who receive initial chemotherapy in the palliative setting while inpatient generally have a poor performance status or high disease burden. However, when patients are diagnosed with a highly chemo-responsive cancer such as small cell lung cancer (SCLC) initiation of inpatient chemotherapy is advised. The outcomes in non-small cell lung cancer (NSCLC) are less understood. To our knowledge, this is the first large-scale study to specifically address overall survival (OS) when initiated first line treatment inpatient vs outpatient for both SCLC and NSCLC. Methods: A retrospective cohort study using the TriNetX Research Network, a federated platform of HIPAA-compliant patient records from 159 healthcare organizations (HCO) from the Global Collaborative Network was carried out. Treatment for SCLC and NSCLC was determined based on NCCN guidelines, immunotherapy was only included for outpatient, assuming it was not administered in the inpatient. Each group was balanced for age at diagnosis and male sex. Kaplan-Meier survival curves were used to assess OS. Results: SCLC Of 4,484 SCLC patients from 36 HCOs (627 inpatient, 3,857 outpatient), 620 patients were identified for each cohort after balancing. OS did not differ for SCLC patients receiving first-line treatment inpatient vs outpatient. At 6-, 12- and 24- months the survival probability of inpatient initiation vs outpatient was noted to be 75% vs 73%, 51% vs 53% and 31% vs 31%, respectively. Patients who started treatment in the outpatient were noted to have less subsequent ED visits (OR 0.264, CI 0.212-0.328) and less hospital admissions (OR 0.167, CI 0.133-0.209). NSCLC: Of 65,375 NSCLC patients (8,704 inpatient/58,066 outpatient) across 35 HCOs, 7,308 per cohort remained after balancing Worse OS was noted in those patients with NSCLC who received their first line treatment inpatient. The survival probability of outpatient was superior at 6, 12 and 24 months with 84%, 72% and 59% (compared to inpatient with 83%, 69% and 54%, respectively). Patients who started treatment in the outpatient were noted to have less ED visits (OR 0.264, CI 0.247-0.282) and less hospital admissions (OR 0.085, CI 0.079-0.092). Conclusions: Analysis reveals no survival difference for SCLC patients initiated on treatment as inpatients vs outpatients, confirming that hospitalization for poor performance status shouldn’t contraindicate palliative chemotherapy in SCLC. Conversely, NSCLC patients initiated as inpatients experienced worse OS. Inpatient treatment for these patients requires careful consideration as the absolute difference in OS was relatively small but there is an increase in healthcare utilization. The appropriateness of inpatient chemotherapy for NSCLC should be evaluated carefully and included in the consideration of goals of care discussion, adjusted treatment regimens, and timely referral to hospice care.

Effectiveness of first-line ET+CDK4/6i continuation beyond disease progression in a large cohort of patients with HR+/HER2− advanced breast cancer: Results from the multicenter, real-world, Italian study PALMARES-2.

1017 Background: Endocrine therapy (ET) plus Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) is the standard 1 st line treatment for patients (pts) with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). ET+CDK4/6i continuation beyond progressive disease (PD) detection, plus/minus locoregional therapies, is often used in clinical practice for selected pts with oligoprogressive disease or minimal PD. However, the effectiveness of this approach has never been investigated in large studies. Methods: In this analysis of the multicenter, real-world study PALMARES-2 (NCT06805812), we evaluated clinical characteristics and outcomes in HR+/HER2- aBC pts who continued 1 st line ET+CDK4/6i after detection of PD, as defined by physicians based on clinical-radiological assessment. The primary endpoint was real-world progression-free survival (rwPFS) beyond PD, defined as the time between the detection of the first PD event during 1 st line ET+CDK4/6i and the occurrence of subsequent PD leading to definitive ET+CDK4/6i discontinuation, or patient death. We used multivariable Cox regression models to explore the association of 15 covariates with rwPFS beyond PD. We also assessed real-world overall survival (rwOS), as defined as the time between 1 st line ET+CDK4/6i initiation and patient death. Results: Of 4,236 consecutive pts who initiated ET+CDK4/6i between January 2016 and September 2024 in 27 Italian Institutions, 2,434 pts experienced a PD event. Of these pts, 454 (18.7%) continued the same ET+CDK4/6i beyond PD and underwent radiotherapy (n = 306; 67%), surgery (n = 39; 9%), other locoregional treatments (n = 28; 6%) or no local therapies (n = 81; 18%). Pts continuing ET+CDK4/6i beyond PD were more likely to be younger and premenopausal, to have higher tumor estrogen receptor (ER) and/or progesterone receptor (PgR) expression, to have bone/lymph node metastases, and less likely to have liver metastases (p < 0.05 for all covariates). Median rwPFS beyond PD was 10.5 months (95% CI: 9.7-12). At multivariable analysis, higher tumor ER (p = 0.031)/PgR (p = 0.001) or lower Ki-67 (p < 0.001) expression, better ECOG Performance Status (p = 0.009) and the use of locoregional treatments (p < 0.001) were associated with longer rwPFS beyond PD. Pts continuing ET+CDK4/6i therapy beyond PD had better median rwOS than those discontinuing it after first PD detection (71.3 and 44.7 months, respectively; p < 0.001). Conclusions: This is the largest real-world study to show the effectiveness of 1 st line ET+CDK4/6i continuation beyond PD in HR+/HER2- aBC pts. Our findings support the use of this well-tolerated and effective approach in selected pts, such as those with less biologically aggressive tumors and/or amenable to locoregional therapies. Clinical trial information: NCT06805812 .

ZAMBONI: A phase II study of zanzalintinib for metastatic clear cell renal cell carcinoma with bone metastases previously treated with immune checkpoint inhibitors.

TPS4634 Background: Bone metastases (BM) in metastatic renal cell carcinoma (mRCC) are associated with aggressive disease behavior and poor prognosis, particularly following progression on immunotherapy (IO)-based treatment regimens. Oral vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitors (TKIs) have demonstrated efficacy in mRCC with BM and have been shown to modulate production of osteoclastogenic factors in the tumor microenvironment. Zanzalintinib is a novel oral VEGFR-targeting TKI that has demonstrated a tolerable safety profile in phase I studies; its broad multikinase targeting profile and short half-life of 16-22 hours may enhance efficacy and tolerability compared with other VEGFR-targeting TKIs. However, the efficacy of zanzalintinib in patients with BM is unknown. Methods: This is a single-institution, phase II trial of zanzalintinib plus investigator-choice bone modifying agent (BMA) in patients with metastatic clear cell RCC with BM that has been previously treated with immunotherapy (IO). Eligible patients will have primarily clear cell histology, at least three BM including at least one BM not previously treated with radiation therapy (RT), and prior disease progression on 1-3 prior lines of therapy including at least one IO-based therapy administered in either the adjuvant or metastatic setting. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is not required. Patients will receive zanzalintinib 60mg by mouth daily in 28-day cycles; treatment will be continued until disease progression or unacceptable toxicity occurs. Dose reduction, re-escalation, or interruption of up to 6 weeks is allowed for patients experiencing adverse events. Investigator-choice BMA may include zoledronic acid, pamidronate, ibandronate, or denosumab, will be administered at a standard dose/interval starting within 30 days of cycle 1, day 1 (C1D1), and continued until criteria for discontinuation of BMA or removal from study are met. RT and/or steroid therapy for symptomatic metastases, including BM, is allowed per investigator discretion. Patients will be radiologically evaluated starting 8 weeks after C1D1 and every 12 weeks thereafter. Adverse events will be monitored throughout the study and for 30 days following cessation of study treatment. Enrollment will continue until 20 patients evaluable for primary endpoint are enrolled, or up to a maximum of 24 patients. The primary endpoint is 12-month landmark progression-free survival and will be evaluated in patients with RECIST-measurable disease at baseline; key secondary endpoints include overall survival, rate of skeletal-related events, and rate of osteonecrosis of the jaw and will be measured in all patients. Clinical trial information: NCT07043608 .