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Association of Medicaid expansion with pre-diagnosis coverage continuity and 2-year overall survival in pediatric patients with blood cancer.

11033 Background: Continuous insurance coverage is critical for timely cancer diagnosis and treatment, yet many patients gain Medicaid only around the time of diagnosis. Although the Affordable Care Act Medicaid expansion targeted adults, it may indirectly influence children via a “welcome mat” effect by increasing outreach and boosting uptake among families with eligible children. The extent to which state expansion status influences Medicaid coverage continuity and survival among Medicaid-insured children with blood cancers—conditions lacking routine screening and often with acute presentation—remains unclear. Methods: Using linked SEER-Medicaid data, we identified 7,536 patients age ≤21 newly diagnosed with leukemia or lymphoma between 2009-2019 who had ≥1 month of Medicaid enrollment from 12 months pre-diagnosis through two months post-diagnosis. Coverage patterns were categorized as: 1) continuous Medicaid (12-13 months enrolled pre-/peri-diagnosis), 2) newly gained Medicaid (enrollment starting at diagnosis or within two months post-diagnosis), and 3) other coverage patterns. Difference-in-differences (DD) models compared post- vs. pre-expansion changes in coverage patterns and 2-year overall survival in 11 SEER expansion states vs. four non-expansion states, adjusting for sociodemographic factors. Survival models additionally adjusted for coverage patterns to assess the extent to which the patterns accounted for expansion-associated survival changes. Results: The percentage with continuous Medicaid increased more in expansion states (52.9% to 67.5%) than non-expansion states (41.5% to 50.8%), leading to a net increase of 8.2 percentage points (ppts; 95% CI = 2.3 to 14.2; p = 0.007) in adjusted DD model. The percentage with newly gained Medicaid decreased more in expansion states (24.6% to 14.2%) than non-expansion states (31.8% to 24.5%), resulting in a net reduction of 7.9 ppts (95% CI = -13.9 to -1.9; p = 0.010). No significant changes were observed post-expansion for other coverage patterns. Two-year overall survival increased in expansion states (85.7% to 86.9%) but declined in non-expansion states (87.7% to 82.9%), yielding a net increase of 6.2 ppt (95% CI = 2.8 to 9.6; p < 0.001) in adjusted DD model. This association was slightly attenuated after further adjusting for coverage patterns (DD = 5.9 ppts; 95% CI = 2.5 to 9.3; p < 0.001), suggesting coverage continuity accounted for approximately 4.9% of the expansion-associated gain in 2-year survival. Conclusions: Medicaid expansion was associated with improved coverage continuity pre-/peri-diagnosis and better early survival among Medicaid-insured children with leukemia or lymphoma. Amid ongoing Medicaid policy changes, these findings add evidence that stable coverage matters for vulnerable children. Future work will evaluate longer-term outcomes (e.g., 5-year survival).

Analysis of delta-like ligand 3 (DLL3) expression levels and characteristics of patients (pts) with advanced extrapulmonary neuroendocrine carcinomas (epNECs) from an ongoing phase I trial.

2642 Background: Specific DLL3 expression on the surface of epNEC tumor cells makes it a promising therapeutic target, but there is a lack of prospective data on DLL3 expression patterns in pts with epNEC. Obrixtamig (BI 764532) is a DLL3/CD3 IgG-like T-cell engager. The first-in-human phase I trial (NCT04429087) showed obrixtamig activity in pts with DLL3-positive epNEC, especially pts with DLL3-high tumors (Capdevila et al, ASCO 2025, #3004). We report updated DLL3 expression data and pt/tumor characteristics in pts with epNEC from NCT04429087. Methods: DLL3 IHC was performed with an investigational DLL3 antibody (SP347) at the Roche CDx CAP/CLIA Laboratory. DLL3 expression was categorized as: negative (absent or weak tumor cell [TC] membrane/cytoplasm staining), positive (moderate-to-strong staining in any TCs), high (≥50% moderate-to-strong TC staining), or low (<50% moderate-to-strong TC staining). Results: As of Sept 4, 2025, 282 of 365 screened pts with epNEC were DLL3-evaluable, of whom 235 (83.3%) had DLL3-positive tumors (DLL3-high: n=120 [42.6%], DLL3-low: n=115 [40.8%]); 47 (16.7%) were DLL3-negative. In the DLL3-positive treated set (n=93), 51 pts (54.8%) had DLL3-high and 42 (45.2%) had DLL3-low tumors. The prevalence of DLL3-high tumors in male/female pts was 47.5%/68.8%, and prevalence in pts with liver/brain metastases was 57.1%/70.0%. DLL3-high prevalence by primary tumor site, GI/GU/cancer of unknown primary site (CUP), was 44.9%/67.7%/60.0%. Pt characteristics in obrixtamig-treated DLL3-high and -low epNEC subgroups are in Table 1. Conclusions: In the largest prospectively screened cohort of pts with epNEC, high (83.3%) prevalence of DLL3 expression was seen, underscoring DLL3 as a promising target for clinical development of DLL3-targeted therapies such as obrixtamig. Obrixtamig safety and efficacy in pts with DLL3-positive epNEC are being assessed in several ongoing trials, including DAREON-5 (NCT05882058), with the data expected to inform and support Phase III development. Clinical trial information: NCT04429087 . DLL3-high (n=51) DLL3-low (n=42) Male / female, n (%) 29 (56.9) / 22 (43.1) 32 (76.2) / 10 (23.8) Primary tumor site: GI / GU / CUP, n (%) 22 (43.1) / 21 (41.2) / 6 (11.8) 27 (64.3) / 10 (23.8) / 4 (9.5) Lactate dehydrogenase ≤ULN / >ULN, n (%) 22 (43.1) / 29 (56.9) 16 (38.1) / 26 (61.9) Prior lines of therapy: 1 / 2 / 3 / >3 12 (23.5) / 17 (33.3) / 9 (17.6) / 13 (25.5) 11 (26.2) / 12 (28.6) / 10 (23.8) / 9 (21.4) Median duration of prior anticancer treatment, weeks (range) 22 (5–349) 22 (8–148) Prior radiotherapy / surgery / anti PD-(L)1, n (%) 22 (43.1) / 28 (54.9) / 14 (27.5) 11 (26.2) / 24 (57.1) / 9 (21.4) Liver / brain metastases, n (%) 40 (78.4) / 7 (13.7) 30 (71.4) / 3 (7.1) Median sum of diameters of target lesions, mm (IQR) 87.5 (64.0–123.0) 117.3 (66.2–176.0)

Dysregulation of the insulin-like growth factor system in non–small cell lung cancer tissue and histologically normal lung tissue in patients with varying degrees of COVID-19 severity.

e20046 Background: The COVID-19 pandemic has created new challenges in oncology, particularly in relation to lung cancer. The insulin-like growth factor (IGF) system is a key regulatory complex involved in carcinogenesis, differentiation, proliferation, and inflammatory processes in the lung tissue. Disruptions in this system have been described in non-small cell lung cancer (NSCLC), acute lung injury, and various infectious diseases. The impact of COVID-19 of varying severity on the IGF system in NSCLC patients is poorly understood. The aim of the research was to study the concentrations of insulin-like growth factors (IGF-I, IGF-II) and their carrier proteins (IGFBP-1, IGFBP-2, IGFBP-3) in tumor tissue and in histologically unchanged resection line tissue in patients with NSCLC who previously suffered from COVID-19. Methods: The study included 60 patients with T1-3NхM0 NSCLC (mean age 59.11±2.9 years), divided into two groups: main (n = 30, moderate/severe COVID-19) and control (n = 30, asymptomatic/mild COVID-19), comparable in age and sex. Levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-2 were measured in tumor and resection margin tissues by ELISA. Statistical analysis used Student's t-test and Mann-Whitney U-test; only significant results (p < 0.05) are reported. Results: In the unchanged lung tissue of patients in the main group it was showed a significant increase in IGF-I levels by 1.6 times in men and by 2.2 times in women, as well as in IGF-II levels by 1.8 times in patients of both sexes, compared to the control group. At the same time, the concentration of IGFBP-2 was increased by 1.3-1.9 times, while the levels of IGFBP-1 did not change significantly. In the tumor tissue of patients in the main group, there was a significant increase in IGF-I level, by 1.7 times in men and by 1.3 times in women, as well as in IGF-II level – by 2.0 and by1.7 times, respectively, against a sharp decrease in IGFBP-1, by 2 times in men and by 6 times in women. At the same time three-fold decrease of IGFBP-2 level was noted only in women. Conclusions: Severe COVID-19 infection led to persistent activation of mitogenic signaling pathways in the lung tissue of patients with NSCLC. The observed increase in IGF-I and IGF-II levels, accompanied by a decrease in IGFBP-1 content, creates conditions for enhanced cell proliferation in both tumorous and morphologically intact tissue. The changes in IGFBP-2 content in women only may indicate a sex-specific mechanisms of regulation in this system. The obtained data explain the possible mechanism of the influence of the infection on the lung cancer progression through the prolonged activation of growth signaling pathways.

Baseline immune and gut microbial–metabolic profiles associated with hepatic immune-related adverse events in lung cancer.

e20605 Background: Hepatic immune-related adverse events (HRAEs) are clinically significant toxicities of immune checkpoint inhibitors in lung cancer with substantial inter-individual heterogeneity. Reliable baseline biomarkers for susceptibility are lacking. The contribution of pre-treatment host immune status and gut microbial and metabolic background to HRAE risk remains insufficiently defined. Methods: We conducted a single-center retrospective observational cohort of n = 70 lung cancer patients receiving PD-1 or PD-L1 inhibitors between January 2022 and June 2025, with biospecimens collected at baseline and at HRAE onset. Patients were followed from treatment initiation until HRAE onset, treatment discontinuation, or end of follow-up, with clinically significant HRAEs defined as Common Terminology Criteria for Adverse Events version 5.0 grade 2 or higher liver injury. Peripheral immune cell subsets, liver function indices, and fecal samples were assessed at baseline. In patients who developed HRAEs, paired immune and fecal samples were analyzed at HRAE onset for immune phenotyping, shotgun metagenomic sequencing, and untargeted metabolomic profiling. Associations with HRAEs were evaluated using logistic regression. Results: Baseline demographic and treatment characteristics were comparable between groups. Prior to treatment, reduced B-cell components and increased helper and naive CD4-positive T-cell proportions, together with intermediate activated T-cell proportions, defined a high-risk baseline immune phenotype for HRAEs. Baseline metagenomic profiling revealed distinct gut microbial community structures between risk states, including differential abundance of Phocaeicola coprocola and Ruminococcus, supporting a pre-existing microbial background for HRAE susceptibility. Untargeted metabolomics demonstrated enrichment of nucleoside-related, fatty acid metabolism–related, and microbiota-derived metabolites in HRAE-susceptible patients, with higher baseline adenosine, palmitoylcarnitine, and phenylacetylglutamine, indicating a coordinated immune–microbial–metabolic background linked to toxicity risk. At HRAE onset, immune changes were dominated by functional activation, with increased activated CD4-positive and CD8-positive T cells and natural killer cell activation, without evidence of systemic immune restructuring. Astilbin exhibited a stage-dependent pattern, with higher baseline levels followed by a decrease at HRAE onset. Conclusions: HRAE susceptibility in lung cancer reflects a pre-existing immune–microbial–metabolic background rather than immune checkpoint inhibitor exposure. Reduced B-cell components and increased helper and naive CD4-positive T-cell features define an immune-susceptible state linked to toxicity risk and may inform pre-treatment risk stratification.

Real-world (rw) study of the treatment journey following antibody-drug conjugate (ADC) initiation and overall survival (OS) in breast cancer (BC) in a US community setting.

e13089 Background: ADCs have transformed the BC treatment landscape by providing clinically meaningful improvements in patient (pt) outcomes. This observational study aimed to describe the pt population, treatment patterns, and outcomes among pts with BC who received ADC treatment in a rw setting. Methods: Based on de-identified, pt-level data in a US community setting from the iKnowMed EHR database (cut off: Feb 28, 2025), this study identified adult pts with BC who initiated a 1st ADC (index ADC) between Jan 2020 and Aug 2024. Real world overall survival (rwOS) from ADC initiation to death from any cause was assessed by BC subtypes and ADC settings. Results: Among 4924 pts with BC who received an ADC, 1880 had HR+/HER2+, 1057 had HR+/HER2−, 666 had HR−/HER2+, 674 had triple-negative breast cancer (TNBC), and 647 had unknown subtype. Pts were predominantly female (99.4%), median age was 60 y (range, 21–≥90), and median follow-up was 14.6 mo (range, 0.1–61.7). At initial diagnosis, 36.7% had stage IV disease. Among 687 pts (14.0%) who received a 2nd ADC, use of trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), and sacituzumab govitecan (SG) as the index ADC was 55, 39, and 34 pts in metastatic regimen 1 (R1); 58, 43, and 36 in R2; and 49, 41, and 30 in R3, respectively. Across metastatic settings, most pts received SG as 2nd ADC after T-DXd, and T-DXd as 2nd ADC after T-DM1 or SG. Among pts receiving ≥2 of any metastatic regimen, 12-mo rwOS ranged from 81.1–91.1% for HR+/HER2+, 79.7–83.3% for HR−/HER2+, 59.3–66.7% for HR+/HER2−, and 54.9–61.4% for TNBC. Median rwOS for pts who received ≥2 of any metastatic regimen was 32.2 mo to not reached for HR+/HER2+, 27.6–38.7 mo for HR−/HER2+, 17.2–18.4 mo for HR+/HER2−, and 12.6–15.4 mo for TNBC. Conclusions: Consistent with contemporary approvals, T-DM1 is largely used for HER2+ BC in the adjuvant setting. T-DXd use becomes more frequent and nearly equal to T-DM1 use for HER2+ BC in R1, but then dominates in R2+. T-DXd is dominant for HR+/HER2− BC across R1-R3+. Survival outcomes among pts receiving ≥2 metastatic regimens highlight meaningful differences by subtype and establish contemporary rwOS reference points for clinical practice and future real-world comparative effectiveness studies. Distribution of index ADC for BC by subtype. ADC Treatment HR+/HER2+ (n = 1880) HR+/HER2− (n = 1057) HR−/HER2+ (n = 666) TNBC (n = 674) T-DM1 T-DXd SG T-DM1 T-DXd SG T-DM1 T-DXd SG T-DM1 T-DXd SG Adjuvant n 1210 8   333   5 100% 100%   100%   100% R1 n 85 80 2 1 87 31 49 55 2 43 153 50.9% 47.9% 1.2% 0.8% 73.1% 26.1% 46.2% 51.9% 1.9% 21.9% 78.1% R2 n 79 89 1 2 108 47 52 86   2 44 162 46.7% 52.7% 0.6% 1.3% 68.8 29.9% 37.7% 62.3%   1.0% 21.2% 77.9% R3+ n 120 205 9 12 568 193 38 43 8 4 35 226 35.9% 61.4% 2.7% 1.6% 73.5% 25.0% 42.7% 48.3% 9.0% 1.5% 13.2% 85.3%

Treatment-related changes in body composition during maximal androgen blockade (MAB) for metastatic hormone-sensitive prostate cancer (mHSPC).

e17097 Background: Androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitors (ARPI) +/- docetaxel is the standard of care for patients with mHSPC. ADT is known to induce adverse body composition changes, including loss of skeletal muscle and increased adiposity, which have been linked to an increased risk of obesity, sarcopenia, fracture and cardiovascular disease. However, the specific effects of MAB (ADT + ARPI) remain poorly defined. Methods: We retrospectively identified patients with mHSPC treated with MAB +/- docetaxel at the Oncology Institute of Southern Switzerland from 2019 to 2025 who underwent a computed tomography (CT) scan before hormonal therapy initiation (T0) and after 6 ± 3 months of ARPI treatment (T1). Automated CT-based body composition analysis (DAFS Express) quantified skeletal muscle area (SMA), visceral (VAT), subcutaneous (SAT), and intramuscular adipose tissue (IMAT) areas and their mean attenuation (density) at L3 level. Paired comparisons were performed between T0 and T1. A multivariable linear mixed model was fitted to assess associations between baseline clinical characteristics (Table 1) and 6-month variations in body composition parameters during treatment. Results: Overall, 192 CT scans from 86 patients were analyzed (Table 1). After six months of ARPI exposure, patients experienced a significant reduction in SMA (mean variation: -7.86 cm 2 , -7.2%, p < 0.001) and derived Skeletal muscle index (p < 0.01), and an increase in SAT (+27.62 cm 2 , +14.8%, p < 0.001) and IMAT (+1.33 cm 2 , +5.6%, p = 0.006), with heterogenous and nonsignificant VAT changes (p = 0.15). Density of SAT (CT attenuation) decreased (p = 0.001), indicating deposition of mature adipose tissue. In the multivariable model, only the specific ARPI used was independently associated with VAT variation (p = 0.017), with enzalutamide linked to a higher probability of a decrease in VAT (p = 0.0063). No other clinical factors significantly influenced the 6-month body composition results. Conclusions: In men with mHSPC, MAB induces significant skeletal muscle loss and increased adiposity within 6 months of therapy. Addition of enzalutamide was associated with a significant VAT reduction, suggesting possible distinct effects of ARPIs on these tissues. Early lifestyle modification (e.g., personalized dietary and exercise interventions) should be incorporated in the clinical routine management for men with mHSPC to actively counteract these effects. Characteristic Study population, N=86 Age, median (range), y 75.8 (54-91) BMI, median (range), kg/m² 26.4 (19.7-38.6) De novo mHSPC, n (%) 70 (81.4) CHAARTED high-volume, n (%) 53 (61.6) ARPI for mHSPC, n (%) Abiraterone 27 (31%), Darolutamide 26 (30%), Enzalutamide 20 (23%), Apalutamide 13 (15%) Added docetaxel in mHSPC to ADT+ARPI, n (%) 8 (9.3%)

Pooled analysis of phase I and expanded access study cohorts of DOC1021 (dubodencel) in combination with chemoradiation for glioblastoma.

2076 Background: Glioblastoma (GBM) is a poor-prognosis brain malignancy with median overall survival (mOS) of ~12-18 months despite aggressive standard of care (SOC) treatment. DOC1021 is an autologous dendritic cell (DC)-based immunotherapy generated by tandem loading with autologous tumor-derived mRNA and lysate, enabling broad antigen presentation. DOC1021 leverages p38MAPK and mTORC1 signaling cascades to initiate cDC1-like skewing of monocyte-derived DC, leading to potent downstream development of CD8 + tissue-homing, cytolytic effector memory cells. Methods: This pooled analysis includes newly diagnosed and recurrent IDH-wt patients from two clinical trials (Phase I Study 8148 [NCT04552886] and Expanded Access Protocol EAP0001), treated with DOC1021 after resection and SOC chemoradiation. DOC1021, prepared from mobilized peripheral blood mononuclear cells (PBMC) loaded consecutively with autologous amplified tumor mRNA and tumor lysate, was administered bilaterally near deep cervical lymph node chains every other week for 3 administrations with weekly pegylated-IFN. Study 8148 (n=18) evaluated 4 dose levels (3.5 x 10 6 to 36 x 10 6 cells), while Study EAP0001 (n=7) administered only the highest dose level (36 x 10 6 cells). Patients with subtotal resection or pre-treatment progression were not excluded. Blood was collected before and after DOC1021 to assess peripheral immune responses. Results: Among the pooled population (N=25), median age was 58 years (range 47-75), 88% MGMT unmethylated, 24% partially resected, and 16% recurrent disease. There were no dose-limiting toxicities, and a similar safety profile between studies. Common AEs included mild, flu-like symptoms and injection-site reactions. One patient in the EAP study experienced grade 3 cerebral edema after the first DOC1021 dose that fully resolved and subsequent DOC1021 doses were completed per protocol. At the time of analysis, 7 of 21 newly diagnosed patients remain alive ~9-30 months post-surgery. Among recurrent patients (n=4), 2 patients remain alive ~16-20 months after second resection. Pseudo-progression within ~6 months of vaccination was commonly observed. Analysis of post-vaccination PBMC indicated expansion of CD4 + (17/20 patients, mean +28.6%, p=0.0006) and CD8 + (15/20 patients, mean +26.8%, p=0.001) central memory T-cell (T CM ) compartments as well as substantial upregulation of CD127 expression on circulating CD8 + T cells (18/20; mean MFI +72.2%, p=0.03). Conclusions: Collectively, the data show that DOC1021 plus SOC is well-tolerated, feasible, and potentially efficacious in a challenging population that included subtotal resections, pre-treatment progression, and majority MGMT unmethylated. A multi-center, randomized, open-label Phase 2 trial (NCT06805305) in newly diagnosed GBM is now enrolling to compare DOC1021+SOC vs SOC treatment alone. Clinical trial information: NCT04552886 .

Endometrial cancer response to pro-EMT effects of type 2 diabetic exosomes.

e22617 Background: According to the International Diabetes Federation, over 151 million adults globally suffer from Type 2 Diabetes Mellitus (T2D). New research is showing that the changes of metabolism that occur during T2D are starting to effect both incidence and progression of certain cancers. Endometrial cancer is one, with patients with T2D have an incidence rate ratio of 1.61 (95% CI, 1.51–1.71) and a mortality risk ratio of 1.32 (95% CI, 1.10–1.60) compared to those without T2D. Recent studies suggest that exosomes might explain this link. In models of prostate and breast cancer—both of which have higher incidences in patients with T2D— cancer cells exposed to exosomes from patients with T2D show increased expression of pro-EMT genes compared to those exposed to nondiabetic (ND) exosomes. Exosomes carry miRNAs that reflect the metabolic status of originating tissues and alter the tumor microenvironment. Given that endometrial cancer is also an epithelial cancer exhibiting a similar dangerous trend in T2D patients, we hypothesize that T2D exosomes will similarly induce epithelial-to-mesenchymal transition (EMT) in endometrial cancer, compared to ND exosomes. Methods: Ishikawa cells, a well-established endometrial cancer cell line, were treated with plasma-derived exosomes from whole blood of patients at Boston Medical Center’s endocrinology clinic, either with or without T2D. After 72 hours of treatment, total RNA was extracted, and qPCR was performed to analyze various EMT genes, including SNAI1, CHD1, CD274, and TWIST. An unbiased array using the Human RT2 Profiler PCR Array of 84 EMT genes was also conducted. Analysis was performed using Ct values normalized to ACTB (ΔCt) to determine the fold change in gene expression. Results: Fluorescent microscopy confirmed exosome uptake and nuclear localization in Ishikawa cells. However, contrary to our hypothesis, T2D exosomes did not induce EMT. Targeted qPCR showed no significant differences in EMT gene expression between T2D and non-diabetic exosome-treated cells. The unbiased array similarly revealed minimal changes, with only SOX11 demonstrating a twofold increase in expression. Conclusions: Despite increased endometrial cancer risk in T2D patients, T2D-derived exosomal miRNAs do not appear to drive EMT in Ishikawa cells. This contrasts with findings in other epithelial cancers and suggests that endometrial cancer cells may possess mechanisms that confer resistance to exosomal miRNA signaling. Identifying these mechanisms may offer novel therapeutic insights for malignancies in which T2D exacerbates tumor aggressiveness.

Systemic therapy for stage IV primary extramammary Paget disease: A systematic review of reported clinical outcomes.

e21564 Background: Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma with limited evidence guiding systemic therapy in advanced or metastatic disease. We conducted a systematic review to characterize patient demographics, metastatic patterns, systemic treatments, and reported outcomes in stage IV primary EMPD. Methods: We performed a systematic review of PubMed/MEDLINE and the Cochrane Database, along with major conference proceedings, from inception through November 2025. Eligible cases included stage IV (M1) disease. Secondary EMPD arising from an underlying malignancy was excluded. Data were extracted at the case level, including metastatic patterns, systemic treatment regimens, and outcomes. The primary outcome was treatment response, categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The objective response rate (ORR; CR + PR) was calculated among cases with reported response data. Analyses were primarily descriptive, with exploratory comparisons performed where feasible, in accordance with PRISMA guidelines. Results: Seventy-five patients with distant metastatic primary EMPD were identified. Median age was 66 years (range, 47–88); 60% were male. Primary tumor sites were most commonly scrotal/penoscrotal (52.0%), followed by vulvar (14.7%) and perianal/perineal (12.0%). Metastatic involvement included bone metastases in 41.3%, visceral metastases in 36.0%, lymph node (LN)-only disease in 25.3%, and skin/scalp metastases in 4.0%. Among cases with reported response data (n = 42), ORR was 64.3%, including CR in 26.2% and PR in 38.1%. Progressive disease occurred in 31.0% of reported cases. Progressive disease rates were higher in patients with visceral metastases compared with those without visceral involvement. Platinum- and taxane-based chemotherapy were the most frequently used regimens, commonly in combination. HER2-targeted therapy was reported in 9.3% of cases and was almost always combined with chemotherapy. No statistically significant association between HER2-targeted therapy and ORR was observed (OR 0.81; p = 1.00), though this analysis was markedly underpowered. Biomarker and safety reporting were inconsistent, with occasional grade ≥3 toxicities and rare treatment-related deaths described. Conclusions: Systemic therapy for stage IV primary EMPD is associated with objective responses in a substantial proportion of reported cases, particularly with platinum- and taxane-based chemotherapy. However, outcomes appear poorer in patients with visceral metastatic disease. Evidence supporting HER2-targeted therapy remains limited by small sample size and reporting bias. Prospective, multi-institutional studies and standardized reporting of biomarkers and outcomes are imperative to define optimal systemic treatment strategies for this rare malignancy.

GLP-1 receptor agonist therapy and cancer risk and mortality in patients with moderate CKD: A national matched cohort study of 58,000 patients.

10583 Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been associated with reduced mortality in patients with Type 2 Diabetes Mellitus (T2DM) and may lower cancer risk. However, the impact of GLP-1 RAs on cancer incidence and mortality in patients with chronic kidney disease (CKD) remains understudied. Thus, in this study we evaluated whether GLP-1 RA use modifies cancer risk and mortality in a contemporary national cohort of patients with moderate CKD. Methods: We performed a retrospective cohort study using the TriNetX Research Network, identifying adults aged 18–90 years with T2DM and newly diagnosed stage-3 CKD between January 2015 and February 2025. Patients with prior malignant neoplasms or end-stage renal disease were excluded. Exposure was defined as a prescription for a GLP-1 RA within 90 days before CKD diagnosis; controls had no documented GLP-1 RA use. Outcomes were evaluated beginning 90 days after the index CKD diagnosis to reduce reverse-causation and immortal-time bias. Our primary outcome was any malignant neoplasm. Our secondary outcomes were site-specific malignant neoplasms (colorectal, lung, liver, kidney, pancreatic, breast, and prostate) as well as all-cause mortality. We performed 1:1 propensity score matching balancing demographics, comorbidities, laboratory values (hemoglobin A1c and estimated glomerular filtration rate), and cardiometabolic medications. After matching, we calculated absolute risks, risk differences, hazard ratios, risk ratios, and 95% confidence intervals. Statistical significance was defined as p < 0.05. Results: After matching, 28,948 patients remained in each group. GLP-1 RA use was associated with significantly lower all-cause mortality (8.6% vs 15.0%; HR 0.57; 95% CI, 0.546-0.599; p < 0.001). Overall malignant neoplasm incidence was significantly lower with GLP-1 RA use (7.0% vs 7.7%; RR 0.90; p < 0.001). Among site-specific malignancies, the GLP-1 RA group demonstrated lower incidence of lung cancer (0.5% vs 0.8%; RR 0.56; p < 0.001), colorectal cancer (0.5% vs 0.7%; RR 0.74; p = 0.006), and liver cancer (0.3% vs 0.4%; RR 0.63; p = 0.001). Pancreatic cancer (0.2% vs 0.3%; RR 0.89; p = 0.46), kidney cancer (0.5% vs 0.6%; RR 0.98; p = 0.87), prostate cancer (1.1% vs 1.0%; RR 1.08; p = 0.32), and breast cancer (0.7% vs 0.7%; RR 1.11; p = 0.30) did not differ significantly based on GLP-1 RA receipt. Conclusions: In patients with T2DM and stage-3 CKD, GLP-1 RA therapy was associated with substantially lower mortality and reduced incidence of several major malignancies, particularly lung, colorectal, and hepatocellular cancers. These findings highlight a potential role for GLP-1–mediated metabolic modulation in cancer prevention among high-risk populations. Prospective studies are warranted to clarify mechanisms and confirm these observations.

Beyond haematological control: Long-term renal outcomes of imatinib therapy in chronic myeloid leukaemia.

6581 Background: Imatinib has transformed outcomes in chronic myeloid leukaemia (CML), enabling long-term survival and durable molecular responses. With therapy often extending over decades, late toxicities affecting organ function have gained increasing importance. However, real-world data on long-term renal outcomes with prolonged imatinib exposure remain limited. Objectives: To evaluate long-term changes in renal function in patients with CML receiving imatinib therapy for at least 10 years. Methods: This retrospective observational study included patients with CML treated with imatinib for ≥10 years at a single tertiary care centre. Clinical and treatment-related data were obtained from medical records. Renal function at baseline and at latest follow-up was assessed using estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Data on diabetes and hypertension were collected. Patients with pre-existing chronic kidney disease, those receiving chemotherapy, those diagnosed with a second malignancy and patients in treatment-free remission (TFR) were excluded. Results: A total of 440 patients were analysed. The median age at diagnosis was 36 years (range, 5–70), with a male-to-female ratio of 1.39:1. At diagnosis, 95% were in chronic phase. Sokal risk stratification classified 32%, 31%, and 37% of patients as low, intermediate, and high risk, respectively. The median duration of imatinib therapy was 15 years (range, 10–24), with a median daily dose of 400 mg (range, 200–800 mg). At last follow-up, 91% of patients had achieved major molecular response. Overall, 62 patients (14%) developed a clinically significant decline in renal function (eGFR <60 mL/min/1.73 m²). In this subgroup, median eGFR declined from 90 range, 70-122) to 44 mL/min/1.73 m² (range, 13-54); representing a median reduction of 46 mL/min over 15 years (approximately 3 mL/min/year). Comorbidities were present in 11 patients (18%). A greater decline in eGFR was observed among males (p<0.001), patients aged <35 years at diagnosis (p<0.0001), and those achieving major molecular response (p<0.0002). Treatment modification was undertaken in<37 patients (60%), including TFR in 13 (21%), dose reduction in 20 (32%), and switching to an alternate tyrosine kinase inhibitor in 4 (6%). Partial renal recovery was documented in 9 patients (24%). All patients in whom TFR was attempted continue to maintain TFR at last follow-up. Conclusions: Long-term imatinib therapy is associated with a gradual but clinically meaningful decline in renal function in a subset of patients with CML. Dose modification, switching TKIs, or attempting TFR may result in partial reversibility, without compromising disease control. These findings highlight the importance of long-term renal monitoring and treatment optimisation in patients with sustained molecular responses.

Efficacy, safety, and immunogenicity of pertuzumab biosimilar versus reference pertuzumab in combination with trastuzumab and docetaxel in HER2-positive metastatic breast cancer: A randomized, double-blind, multicenter, parallel group, phase III clinical trial.

1047 Background: Pertuzumab plus trastuzumab and docetaxel is a standard first-line treatment regimen for HER2-positive metastatic breast cancer (MBC). This phase III trial evaluated the therapeutic equivalence of pertuzumab biosimilar (manufactured by Intas Pharmaceuticals Ltd., Ahmedabad, India) versus Perjeta when combined with trastuzumab and docetaxel. Methods: This was a randomized (1:1), double-blind, multicenter, parallel-group, phase III equivalence study. Adults with HER2-positive MBC were enrolled and received pertuzumab I.V. (biosimilar or reference product) 840 mg loading dose in cycle 1, then 420 mg every 3 weeks for 24 weeks, in combination with trastuzumab and docetaxel as first-line therapy. Primary endpoint was independently assessed objective response rate (ORR) at week 24 per RECIST v1.1. Secondary endpoints included PFS, OS, duration of response, time-to-event outcomes, pharmacokinetics (T max , C max , AUC 0-t ), safety, and immunogenicity (anti-drug antibodies, ADA). Results: A total of 213 patients were randomized (pertuzumab biosimilar n=106; reference product n=107). ORR at week 24 was comparable between the biosimilar and reference pertuzumab arms: in the mITT set, ORR was 71.3% (72/101) versus 65.0% (67/103), respectively. 6-months PFS rate was 90.1% vs 89.3% in biosimilar and reference pertuzumab arms respectively. Pharmacokinetic parameters (T max , C max , AUC 0-t ) and immunogenecity were comparable between both the arms. Treatment-emergent adverse events (AEs) occurred in 65.1% (pertuzumab biosimilar) and 72.9% (reference product) of patients; most common AEs observed in ≥5% patients in pertuzumab biosimilar vs reference product arm were the following: diarrhea (32.1% vs 30.8%), alopecia (17.0% vs 12.1%), anaemia (8.5% vs 18.7%), vomiting (10.4% vs 11.2%), pyrexia (8.5% vs 10.3%), fatigue (8.5% vs 7.5%), neutropenia (6.6% vs 8.4%), leukopenia (6.6% vs 8.4%), nausea (4.7% vs 7.5%), cough (4.7% vs 5.6%) and headache (3.8% vs 5.6%). Conclusions: Pertuzumab biosimilar demonstrated therapeutic equivalence to reference product in combination with trastuzumab and docetaxel for first-line HER2-positive MBC. Efficacy, safety, pharmacokinetic similarity, and comparable immunogenicity support biosimilarity and its potential as an effective treatment option. Clinical trial information: CTRI/2022/12/048133. Summary statistics for objective response rate (ORR) at week 24 (mITT set, N=204). Parameter Pertuzumab biosimilar (N=101), n (%) Reference product (N=103), n (%) Complete response 4 (4%) 1 (1%) Partial response 68 (67.3%) 66 (64.1%) Overall response rate 72 (71.3%) 67 (65.0%) Difference in ORR (95% CIs) -7.50, 19.97

FOLFIRINOX vs gem/pac in the elderly: Is the survival benefit worth the risk?

e16420 Background: FOLFIRINOX (FFX) is standard first-line therapy for metastatic pancreatic adenocarcinoma (mPDAC) but is often avoided in elderly patients due to toxicity concerns, with Gemcitabine plus Nab-Paclitaxel (GP) frequently preferred. Comparative real-world data on survival and healthcare utilization (HCU) in elderly patients are limited. Methods: We performed a retrospective cohort study using the TriNetX Global Health Research Network. Patients aged ≥75 years with mPDAC treated with first-line FFX or GP through January 15, 2026 were identified. Propensity score matching (1:1 greedy nearest-neighbor, caliper 0.1) balanced baseline characteristics. Outcomes included 1-year overall survival (OS), 90-day safety events, and 90-day HCU. Subgroup analyses were performed for patients with CA19-9 > 1000 U/mL. Kaplan-Meier survival analysis and log-rank tests were used. Results: A total of 970 matched patients were included (485 per group). FFX was associated with improved 1-year OS compared with GP (57.1% vs 48.5%, p = 0.02). Median OS was not reached in the FFX group versus 11.7 months with GP. The hazard ratio for 1-year mortality favored FFX (HR 0.79; 95% CI 0.65–0.96) but was not statistically significant. No significant differences were observed in 90-day safety or HCU. Sepsis/septic shock occurred less frequently with FFX (8.2% vs 11.1%, p = 0.13). Hospitalization (35.3% vs 34.8%) and ICU admission (7.6% vs 5.8%) rates were similar. Among patients with CA19-9 > 1000, safety, HCU outcomes, and OS similarly favored FFX without increased toxicity. Conclusions: In elderly patients with mPDAC, first-line FOLFIRINOX was associated with improved survival without increased short-term toxicity or healthcare utilization, even among those with poor prognostic CA19-9 levels. These findings support FFX as a viable option for carefully selected elderly patients, though lack of functional status matching suggests possible selection of fitter individuals. Outcome FOLFIRINOX cohort (n=485) (purple) Gem/ Pac cohort (n= 485) (green) Hazard Ratio/ Risk Ratio (95% CI) p-value 1- year Overall Survival 0.79 (0.65 – 0.96) 0.66 Deceased 180 215 Survival Probability 57.1% 48.5% 0.02 Median Survival Not reached 11.7 months 90-day healthcare utilization Any hospitalization 171 (35.3%) 169 (34.8%) 1.012 (0.853, 1.201) 0.89 ICU admission 37 (7.6%) 28 (5.8%) 1.321 (0.822, 2.124) 0.25 90-daysafety outcomes Sepsis/ Severe Sepsis/ Septic shock 40 (8.2%) 54 (11.1%) 0.741 (0.502, 1.093) 0.13 Survivability CA19-9>1000 U/ml cohort FOLFORNIOX(n 109) 1 year survival %: 60.1 Gem/Pac (n 109) 1 year survival %: 44.3% **Hazard ratio 0.64 (0.43-0.95) 0.024

Diagnostic accuracy of circulating tumor DNA for post-remission surveillance in diffuse large B-cell lymphoma: A systematic review and meta-analysis.

7060 Background: Relapse after complete remission remains a major cause of treatment failure in Diffuse Large B-Cell Lymphoma (DLBCL). Standard surveillance using clinical assessment and imaging often detects recurrence after substantial tumor regrowth. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for minimal residual disease detection; however, its diagnostic accuracy for relapse surveillance in DLBCL has not been systematically quantified. Methods: A systematic review and meta-analysis was performed per a prespecified PROSPERO protocol (CRD420251179858). MEDLINE, Embase, CENTRAL, and major conference proceedings were searched through October 2025. Following systematic screening of B-cell non-Hodgkin lymphoma studies, those eligible for quantitative synthesis enrolled adults with DLBCL in complete remission undergoing post-treatment ctDNA surveillance, with clinically or radiologically confirmed relapse as the reference standard. Studies were included if sufficient data were available to construct 2×2 contingency tables. Pooled sensitivity and specificity were estimated using a bivariate random-effects logistic regression model with a logit link, accounting for between-study heterogeneity. A continuity correction of 0.5 was applied to all cells in studies with zero counts prior to model fitting. Results: Three studies (N=157) comprising patients in complete remission after first-line therapy were included in the quantitative synthesis. Using a bivariate random-effects model, the pooled sensitivity of ctDNA for detection of clinical relapse was 58.6% (95% CI 32.2–80.8%), while pooled specificity was 93.9% (95% CI 83.6–97.9%), indicating high specificity but moderate sensitivity during surveillance. Specificity was consistently high, supporting strong rule-in performance. Sensitivity varied across studies (range: 31%–88%), likely reflecting differences primarily in sampling density, as well as assay platforms (tumor-informed Ig-HTS vs. targeted NGS). Across included cohorts, ctDNA positivity generally preceded or coincided with clinically detected relapse, while ctDNA negativity was associated with durable remission during follow-up. Conclusions: In patients with DLBCL in complete remission after first-line therapy, ctDNA surveillance demonstrates very high specificity but only moderate sensitivity for detection of clinical relapse. These findings support ctDNA as a highly specific rule-in biomarker for relapse during surveillance, potentially resolving ambiguity in equivocal imaging findings. However, its moderate sensitivity limits its standalone ability to detect relapse. Prospective validation of standardized testing intervals and assay harmonization are needed to optimize sensitivity before integration with standard monitoring strategies.

Cost of cytokine release syndrome in patients treated with tarlatamab for extensive-stage small cell lung cancer based on first-line treatment.

e13554 Background: Tarlatamab is a second-line treatment for extensive-stage small cell lung cancer (SCLC) and has changed care for this condition. One factor affecting first-line treatment decisions is overall treatment cost. In this study, we examined the real-world frequency of cytokine release syndrome (CRS) in patients who received tarlatamab and compared the first-line treatments and estimated CRS costs for each. Methods: This was a retrospective cohort analysis using TriNetX Research Network data from the Global Collaborative Network. We included lung cancer patients treated with tarlatamab after atezolizumab (with or without lurbinectedin) or durvalumab. We compared rates of CRS, ICANS, and use of tocilizumab, dexamethasone, or methylprednisolone within 24 hours of tarlatamab using age-adjusted Cox regression analysis. The difference between hospitalization with and without CRS, and the cost of CRS treatment, was acquired from previously reported data from the National Inpatient Sample and Vizient. Expected per-patient costs were estimated by applying age-adjusted hazard ratios for tocilizumab and corticosteroid exposure to baseline CRS rates. Cost uncertainty was derived using 95% confidence intervals of the hazard ratios. Results: The rates of CRS in this study were similar in all the patients, irrespective of their initial treatment. The rates of ICANS were not significantly different in any group. The estimated cost of CRS was highest in the group treated with atezolizumab and lurbinectedin. Higher rates of CRS were noted in the patients in this cohort. The estimated cost of CRS was slightly lower in the durvalumab cohort than in the group treated with atezolizumab. There were slightly lower CRS rates and use of tocilizumab in the durvalumab group. However, the predicted difference in CRS cost between the patients treated with atezolizumab or durvalumab was not significant. Conclusions: The overall cost of treatment in the extensive-stage SCLC remains important to consider. However, the decisions made in the first-line setting do not appear to affect the cost of CRS treatment following tarlatamab. Atezolizumab Atezolizumab + Lurbinectidin Durvalumab n (%) HR (95% CI) n (%) HR (95% CI) n (%) CRS 51/139 (36.7) 1.031 (0.657, 1.619) 37/91 (40.7) 1.018 (0.649, 1.598) 35/98 (35.7) ICANS 24/139 (17.3) 0.817 (0.413, 1.614) 15/91 (16.5) 1.037 (0.537, 2.002) 16/98 (16.3) Tocilizumab 18/51 (35.3) 1.165 (0.576, 2.355) 11/37 (29.7) 0.854 (0.399, 1.825) 12/35 (34.3) Steroids 39/51 (76.5) 1.116 (0.685, 1.819) 28/37 (75.7) 1.39 (0.862, 2.241) 32/35 (91.4) Tocilizumab & Steroids 18 -- 10 -- 11 CRS cost* $87,740 -- $96,342 -- $86,161 Predicted Difference* -- $3,849 (-$30,572, $59,826) -- $1,429 (-$31,943, $55,675) -- *Per patient treated with tarlatamab.

Insurance-related disparities in emergency department presentation among hospitalized colorectal cancer patients: A national analysis.

e15682 Background: Insurance status may influence how and when patients with colorectal cancer (CRC) access care, leading to emergency department (ED)–based hospitalizations rather than planned admissions. We evaluated insurance-related disparities in ED-based admission and in-hospital mortality among CRC patients. Methods: Using the National Inpatient Sample (2018–2020), we identified adults hospitalized with CRC (ICD-10-CM codes C18–C20), excluding inter-hospital transfers and history-only codes. Insurance was categorized as private (reference), Medicare, Medicaid, and other (self-pay/no charge/other). ED-based admission was defined as hospital admission originating in the ED rather than direct or elective admission. Survey-weighted multivariable logistic regression examined associations between insurance type and (1) ED-based admission and (2) in-hospital mortality, adjusting for demographics, income quartile, comorbidities, and hospital characteristics. We assessed whether accounting for ED admission patterns reduced insurance-related mortality differences. Results: Among 421,350 CRC hospitalizations, ED admission rates varied significantly by insurance: private 25%, Medicare 33%, Medicaid 35%, and other 40% (p < 0.0001). After adjustment, odds of ED-based admission were substantially elevated for the other (self-pay/no charge/other) group (aOR 1.96, 95% CI 1.81–2.12), Medicaid (aOR 1.70, 1.60–1.81), and Medicare (aOR 1.37, 1.30–1.44) versus private insurance. In-hospital mortality was higher for the other insurance group (aOR 1.97, 95% CI 1.59–2.44), while Medicaid mortality was similar to private and Medicare showed slightly lower adjusted mortality. Accounting for ED admission patterns modestly reduced excess mortality for the other group (from aOR 1.97 to 1.81, ~17% attenuation). Notably, ED-based admission itself was associated with lower in-hospital mortality (aOR 0.51, 95% CI 0.46–0.57), likely reflecting case-mix differences in direct admissions. Conclusions: Substantial insurance-related disparities exist in how CRC patients enter the hospital, with ED-based admission markedly more common among publicly insured and uninsured patients. However, admission patterns explain only a small portion of mortality disparities, and ED admissions were paradoxically associated with lower mortality. These findings suggest that barriers to timely pre-diagnostic care contribute to emergency presentations, while survival disparities likely reflect upstream factors (stage at presentation) and downstream factors (treatment intensity and care coordination). Expanding insurance coverage, strengthening navigation for abnormal screening or diagnostic findings, and improving urgent outpatient evaluation pathways may reduce preventable emergency presentations and advance equity in CRC outcomes.

BRCA-P: Can denosumab reduce breast cancer risk in <i>BRCA1</i> mutation carriers?

TPS10630 Background: The likely ‘cell-of-origin’ that leads to breast cancer in BRCA1 mutation carriers is a progenitor cell that is highly proliferative and prone to DNA damage. This progenitor cell expresses RANK ligand receptor [RANK] and is hyper-responsive to progesterone through paracrine signaling mediated by RANK ligand [RANKL]. Notably, high tissue expression of RANKL has recently been found in mechanosensitive (stiff) breast tissue and is associated with increased breast density, a recognized breast cancer risk factor. Methods: The BRCA-P trial is a randomized, double-blinded, placebo-controlled multi-centre international phase 3 trial evaluating the RANKL inhibitor denosumab as a possible breast cancer risk-reducing agent (EudraCT 2017-002505-35; NCT04711109). The safety profile of denosumab is generally well understood, as it is currently approved for the treatment of osteoporosis, bone metastases and giant cell tumor of bone. The study is led by the ABCSG (Austria), in collaboration with individual country sponsors in seven participating countries. Eligible participants include women age 25-55 years who carry a BRCA1 pathogenic variant, are unaffected by breast or ovarian cancer, and are not pregnant or currently trying to become pregnant. Participants must also have not undergone prophylactic bilateral mastectomy or be currently taking a chemopreventive agent such as tamoxifen. They are randomised 1:1 to receive either denosumab 120 mg or placebo subcutaneously every 6 months for 5 years. The study primary objective is to evaluate the reduction in the risk of any breast cancer (invasive or DCIS). The safety profile and tolerability of denosumab in this setting will be also studied. Secondary and exploratory objectives include reduction in risk of ovarian, fallopian tube and other cancers, reduction in mammographic breast density, reduction in clinical fractures, effects on bone health and bone turnover markers and quality of life. BRCA-P completed its recruitment phase in December 2024, with 364 participants randomised globally. This investigator-initiated study is supported by Amgen. Clinical trial information: NCT04711109 .

Efficacy and safety of anamorelin in patients with non–small cell lung cancer and cancer cachexia undergoing chemoimmunotherapy: A real-world prospective cohort study (SPIRAL-ANA).

8592 Background: The efficacy and safety of combining anamorelin with chemoimmunotherapy for non–small cell lung cancer (NSCLC) complicated by cancer cachexia remain unclear. This study aims to clarify the potential clinical benefits of combining anamorelin with standard first-line treatment in this challenging patient subpopulation. Methods: We prospectively enrolled patients with advanced NSCLC who had cancer cachexia and were scheduled to initiate anamorelin together with chemoimmunotherapy. Cancer cachexia was defined according to the eligibility criteria for anamorelin administration in Japan. Anamorelin is indicated for patients with body weight loss of ≥5% within the previous 6 months and with anorexia, who meet at least two of the following criteria: 1) fatigue or malaise, 2) generalized muscle weakness, or 3) C-reactive protein level &gt;0.5 mg/dL, or albumin level &lt;3.2 g/dL, or hemoglobin level &lt;12 g/dL. Progression-free survival (PFS) from start of chemoimmunotherapy was the primary endpoint. Results: Overall, 123 patients were enrolled, of whom 118 comprised the safety analysis set and 114 comprised the full analysis set. The median duration of anamorelin treatment was 13.15 weeks. Median age, body weight, and body mass index were 73 years (range: 42–89 years), 53.2 kg (range: 32.5–79.4 kg), and 20.2 kg/m 2 (range: 15.0–29.1 kg/m 2 ), respectively. Among these patients, 20 (17.5%) had an Eastern Cooperative Oncology Group performance status of 2. At week 12, 62 patients (54.4%) were still being treated with anamorelin. The median PFS and overall survival (OS) were 6.2 months and 18.5 months, respectively, and the study did not meet the prespecified PFS endpoint. In a 12-week landmark analysis stratified by cachexia status at week 12, OS was significantly longer in patients who had achieved cachexia improvement by week 12 than in those who remained cachectic (19.9 months versus 7.1 months, log-rank p = 0.0098; hazard ratio for death, 2.19; 95% confidence interval, 1.19–4.02). The safety profile was manageable, with grade ≥3 neutropenia and hyperglycemia occurring in 31.4% and 5.1% of patients, respectively, and no deaths were considered related to anamorelin. Conclusions: In this prospective real-world cohort of patients with NSCLC and cancer cachexia receiving first-line chemoimmunotherapy, anamorelin was associated with a manageable safety profile but did not achieve the primary endpoint of PFS prolongation. Cachexia improvement at week 12 was observed in a substantial proportion of patients and was associated with longer OS. These findings suggest that the clinical value of anamorelin in this setting may lie in facilitating cachexia improvement.

Biogenic iron oxide nanoparticles synthesized from Padina gymnospora: Phytochemical screening, morphological characterization, and thermal stability

Multifunctional Conjugated Ligands Synergistically Optimize the Interface and Regulate Crystallization for High‐Performance 2D/3D Perovskite Solar Cells

ABSTRACT The interfacial optimization of self‐assembled monolayers (SAMs) and precise regulation of perovskite crystallization process are crucial for improving the performance and stability of inverted perovskite solar cells (PSCs). Herein, we designed two multifunctional conjugated cationic ligands (TDZI and TzTzI) to modify the SAMs/perovskite interface. This study reveals that the conjugated ligands form tighter and ordered π–π stacking with [4‐[(3,6‐dimethyl‐9H‐carbazol‐9‐yl) butyl] phosphonic acid (Me‐4PACz), efficiently suppressing Me‐4PACz aggregation. Meanwhile, ligands dissolved in the perovskite precursor induce the bottom‐up growth of 2D/3D heterojunction, which effectively regulates perovskite crystallization process and suppresses defect formation, thereby yielding high‐quality and uniform perovskite films. These synergistic effects enhance the adhesion of SAM/perovskite interface, reduce interfacial non‐radiative recombination loss, and accelerate the extraction and transport of carriers. Finally, the inverted PSCs modified with TzTzI achieved an exceptional power conversion efficiency (PCE) of 26.61% with a high open‐circuit voltage ( V oc ) of 1.204 V, which is among the highest efficiencies reported to date for 2D/3D heterojunction PSCs. Moreover, the unencapsulated devices exhibit excellent humidity, thermal and operational stability under the ISOS protocols. Excitingly, the TzTzI‐based PSCs delivered outstanding PCEs of 24.5% for 1 cm 2 devices, 20.61% for devices with 1.72 eV bandgap, and 22.14% for mini‐modules.