Browse Articles

Real-world feasibility and hematologic toxicity of induction chemotherapy in advanced cervical cancer in a resource-limited setting.

e13634 Background: Induction chemotherapy has reshaped the treatment paradigm for locally advanced cervical cancer (LACC), demonstrating overall survival benefit. However, feasibility and toxicity management may be challenging in low-resource settings, potentially limiting reproducibility. Real-world data from these contexts are needed. Methods: This retrospective observational study included women ≥18 years with cervical cancer stages IB3–IVA (FIGO 2018) treated per the INTERLACE protocol in a low-resource population (January 2024–June 2025). Induction chemotherapy consisted of weekly carboplatin (AUC 2) and paclitaxel (80 mg/m²) for six weeks, followed by 3D conformal radiotherapy with concurrent weekly cisplatin and intracavitary brachytherapy (2D point A). Clinical-pathological data, treatment adherence, toxicity (CTCAE v5.0), and MRI-based response were collected. Analysis was descriptive. Results: Thirty-five patients were evaluated (median age 43.4 years). Squamous carcinoma predominated (85.7%), and 71.4% had stage II disease. Six induction cycles were completed in 80% of patients; 82.9% received ≥5 cycles. Median time to radiotherapy was 12 days (7–55). Concurrent cisplatin (≥5 cycles) was completed by 54.3%. Grade 3–4 hematologic toxicity occurred in 20% during induction and 22% during chemoradiotherapy. Anemia occurred in 77.1% (G3–4:12%) and 91.1% (G3–4:6%), respectively; 57.1% required transfusion. Grade 3–4 neutropenia occurred in 22%, including two cases of febrile neutropenia. Toxicities were manageable, with no treatment-related deaths. The overall response rate was 88.5%. Conclusions: In a resource-limited public system, INTERLACE implementation demands structured planning and close monitoring. High hematologic toxicity and transfusional needs underscore care delivery challenges, and suboptimal local treatment may affect long-term outcomes. Grade 3–4 treatment-related adverse events. Toxicity During Induction Chemotherapyn (%) During Concurrent Chemoradiotherapyn (%) Grade 3–4 hematologic adverse events 7 (20) 8 (22) Neutropenia 3 (8) 5 (14) Anemia 4 (12) 2 (6) Thrombocytopenia 0 1 (3) Any grade 3–4 non-hematologic adverse event 4 (11) 0 Bronchospasm 1 (3) 0 Diarrhea 1 (3) 0 Infection 1 (3) 0 Peripheral neuropathy 1 (3) 0

Genomic profiling of diffuse intrinsic pontine glioma in AACR Project GENIE.

e14070 Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive high-grade glioma, originating in the pons and primarily affecting children <10 years of age. Surgical resection is rarely feasible and median survival with radiation remains <1 year. Prior studies indicate histone H3 epigenetic dysregulation driving DIPG but data are limited to small institutional cohorts. This study leverages the American Association for Cancer Research (AACR) Project Genomic Evidence Neoplasia Information Exchange (GENIE) database to characterize DIPG’s mutational landscape and identify possible therapeutic targets. Methods: The AACR Project GENIE database was accessed from cBioPortal (v18.0-public) on November 25, 2025 to identify patients and samples with confirmed DIPG. Somatic point mutations, copy number alterations, demographic correlations, and mutual exclusivities were analyzed using a two-sided T-test and non-parametric tests, with Benjamini-Hochberg False Discovery Rate correction. Unknown and Other values were excluded. Results: The cohort comprised 240 DIPG samples from 227 patients. Males (n=106, 46.7%) and females (n=113, 49.8%) were similarly affected, and most patients were pediatric (n=197, 86.8%). By race, the cohort consisted of White (n=72, 31.7%), Black (n=16, 7.0%), and Asian (n=12, 5.3%) patients. Samples were collected from primary (n=202, 84.2%) and metastatic (n=12, 5.0%) tumors. The most frequent somatic mutations were observed in H3F3A (n=173, 72.1%), TP53 (n=116, 48.3%), ATRX (n=37, 15.4%), PIK3CA (n=35, 14.6%), PPM1D (n=34, 14.2%), NF1 (n=31, 12.9%), TERT (n=29, 12.1%), ACVR1 (n=29, 12.1%), and HIST1H3B (n=25, 10.4%). Sex-stratified analysis demonstrated a higher frequency of ACVR1 mutations in females compared to males (n=21 vs. n=8; p<0.05), while KMT2C mutations were more frequent in males (p<0.05). Race-based analysis identified several genes detected exclusively in Black patients, including LRP1B , MAP3K9 , and ERBB3 (p<0.01), and BRCA2 mutations were more frequent in Black patients compared with Asian and White patients (p<0.05). In Asian patients, ZFPM1 and RET mutations were observed exclusively (p<0.05). Among frequently altered genes, H3F3A and TP53 mutations demonstrated significant co-occurrence (p<0.05). Stratification by tumor site demonstrated increased prevalence of SLX4 and TET1 mutations in primary tumors (p<0.001), while PIK3R2 mutations were more frequent in metastatic samples (p<0.05). Conclusions: This study demonstrates H3F3A as a key molecular driver of DIPG, highlighting the role of histone H3 epigenetic dysregulation in prior studies. Co-occurrence of H3F3A and TP53 suggests cooperative oncogenic pathways. Sex-based differences (e.g., ACVR1 and KMT2C ) and race-specific alterations emphasize demographic influence on molecular heterogeneity. These results further support H3F3A and its signaling pathways as therapeutic targets in DIPG.

Phase Ib results from the phase Ib/II study of [ ¹⁷⁷ Lu]Lu-DOTA-TATE in combination with standard of care as a first-line treatment for pts with extensive-stage small cell lung cancer.

3010 Background: Most pts with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) relapse after initial response to standard of care (SOC; platinum/etoposide + anti–programmed death-ligand 1 [PD-L1] therapy); novel combination strategies are needed. This Phase Ib/II study (NCT05142696) assessed [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-DOTATATE) – a radioligand therapy with high affinity for somatostatin receptor 2 (SSTR2; a poor prognostic biomarker expressed in ~50% of SCLC tumors) – plus SOC. Here, we report Phase Ib data (cutoff 20 Nov 2025). Methods: Phase Ib was a dosage escalation study to determine the recommended dosage (RD) of 177 Lu-DOTATATE – alongside carboplatin AUC 5 + etoposide 100 mg/m 2 + anti–programmed cell death protein 1 (PD-1)/PD-L1 therapy (pre/post protocol amendment: tislelizumab 200 mg/atezolizumab 1200 mg, respectively) Q3W in the induction phase, and alongside anti–PD-1/PD-L1 therapy Q3W in the maintenance phase – in pts aged ≥18 y with newly diagnosed SSTR+ (by PET/CT) ES-SCLC. Cohorts of 3–6 pts were enrolled to increasing dosage levels (DLs) of 177 Lu-DOTATATE (backfill allowed to ≤10 pts); escalation was guided by dosage-limiting toxicity (DLT) rate (Bayesian Optimal Interval design) and other safety data. The primary endpoint was DLTs ( 177 Lu-DOTATATE–related adverse events within the 42-day DLT period). Results: Of 57 pts screened, 29 received treatment (median [range] age 62 [43–73] y; white 89.7%; male 44.8%; ECOG PS 0/1/2 37.9%/58.6%/3.4%; smoking history 100%; bone/brain/liver metastases 51.7%/13.8%/48.3%); 93.1% completed the induction phase (DL1 [3.7 GBq] 9/9; DL2a [5.55 GBq] 11/11; DL3a [7.4 GBq] 7/9). Median treatment duration between first/last dosage and cutoff was 14.2/9.4 months. For 177 Lu-DOTATATE, median (range) number of doses was 4.0 (1.0–7.0), duration was 4.1 (1–6) months, and cumulative activity was 22.7 (7.1–44.4) GBq. There were no DLTs in 17 evaluable pts. The table reports safety and preliminary efficacy data. Conclusions: The observed safety profile was consistent with expected toxicity; the RD for Phase II was 7.4 GBq. Clinical trial information: NCT05142696 . Safety and preliminary efficacy (N=29). AEs, % Any: all grades; Grade ≥3 100; 100 Treatment related 100 177 Lu-DOTATATE related 86.2* Serious 72.4 † Leading to discontinuation 24.1 ‡ Deaths due to AEs, n 2 § Confirmed best overall response, % 82.8 ¶ 6-month duration of response rate, % 28.5 (95% CI 11.8, 47.7) 6-month progression-free survival rate, % 36.1 (95% CI 19.0, 53.6) *Most commonly reported: thrombocytopenia (58.6) and anemia (44.8). † 66.7 DL1, 63.6 DL2a, 88.9 DL3a. ‡ 33.3 DL1, 27.3 DL2a, 11.1 DL3a. § DL1: cardiac failure, large intestinal hemorrhage (on-treatment death); not treatment related. ¶ 100 DL1, 90.9 DL2a, 55.6 DL3a. AE, adverse event; CI, confidence interval; DL, dosage level.

Prevalence of homologous recombination repair deficiencies in prostate cancer in the Russian Federation.

e17062 Background: Homologous recombination repair (HRR) deficiency represents a frequent and clinically significant molecular event in prostate cancer (PC). The reported prevalence of HRR pathway alterations in metastatic prostate cancer (mPC) cohorts from international studies ranges from 15% to 33%, with germline variants accounting for a considerable subset of these alterations. The observed frequency, however, is not uniform globally; it is influenced by regional disparities in diagnostic accessibility and different clinical guidelines. HRR pathway alterations are associated with more aggressive disease and significantly influence both prognosis and sensitivity to PARP inhibitors and platinum-based therapies. The aim of the research was exploration of the spectrum and frequency of somatic and germline mutations in patients with PC within the Russian population. Methods: 6,447 patients with histologically confirmed PC were tested for germline and somatic variants in HRR-related genes as the part of national genetic testing program launched by the Russian Society of Clinical Oncology (RUSSCO)— “Improving Molecular-Genetic Diagnostics in the Russian Federation (2020–2025)”. 93.2% from them were mPC. 5 050 FFPE tumor samples (78,3%) and 1397 whole blood samples (21,7%) were successfully tested using next generation sequencing assays (Atlas Solo-test HRR panel (2,858 – 44.33%), AmoyDx HANDLE HRR NGS Panel, 24 (1,083 – 16.8%), Atlas Solo-test АВС panel (54 – 2.39%), laboratory-developed test (2,352 – 36.49%). Results: We identified 899 alterations in FFPE samples (17,8%) and 132 in whole blood samples (9,4%). In 19 FFPE samples we detected more than one aberration. A list of altered HRR genes in tested HRR related genes is presented in table. Conclusions: This dataset represents the largest registry of HRR alterations in mPC in the Russian Federation to date. Expanding access to genetic testing offers a valuable opportunity to personalize treatment strategies for mPC. Thus, this population-specific data analysis enables the stratification of patients based on their predicted sensitivity to targeted therapies, which may meaningfully improve their clinical prognosis. A list of altered HRR genes. Genetic alteration FFPE tumor samples/№ FFPE tumor samples/% Whole blood samples/№ Whole blood samples/% ATM 225 25.0 17 12.9 BRCA1 100 11.1 3 2.3 BRCA2 222 24.7 43 32.6 BRIP1 24 2.7 1 0.8 CDK12 91 10.1 0 0 CHEK2 114 12.7 57 43.2 PALB2 44 4.9 6 4.5 RAD51B/C/D 26 2.9 0 0 Other alterations 53 5.9 5 3.8 Total 899 132

A qualitative study of midlife women with type 2 diabetes in the UK: Exploring the impact of diabetes on their well-being

Background and aims Type 2 Diabetes mellitus (T2DM) substantially influences the overall well-being and quality of life of individuals with diabetes and is widely associated with psychosocial burden. However, existing qualitative literature has largely focused on general adult populations, with limited attention to how illness experiences are shaped by gender and life-stage, particularly among midlife women in the UK. Moreover, the ways in which T2DM is integrated into identity, relationships, and future orientation during midlife remain insufficiently theorised. This study aimed to generate an in-depth, interpretive understanding of how midlife women with T2DM experience and make sense of the psychosocial, emotional, and self-management dimensions of the condition in their everyday lives. Methods A qualitative study using online semi-structured interviews. Participants were recruited through a national social media campaign and an established research engagement database. Interviews were conducted with 13 midlife women with type 2 diabetes. Data were analysed using reflexive thematic analysis within an interpretivist framework. Results The main four themes identified were Living with Type 2 Diabetes: encapsulates the practical aspects of living with diabetes, psychosocial dimensions: explores the broader impact of diabetes on participants’ lives, healthcare and support: sources for managing diabetes effectively and lastly outlook and personal development: captures participants’ perspectives on their treatment, their worries about the future, and the unexpected positive outcomes of living with diabetes. Together, these themes illustrate a dynamic process through which participants actively negotiate, reinterpret, and integrate T2DM within the context of midlife transitions, highlighting the interplay between illness, identity, and social roles. Conclusion The findings highlight the need for a multifaceted approach to addressing the barriers and facilitators of diabetes care. This study extends existing qualitative literature by offering a life-stage- and gender-sensitive conceptualisation of living with T2DM, emphasising midlife as a critical period of identity renegotiation and future reorientation. By incorporating patients’ perspectives into care, they may enhance diabetes self-management and support more responsive, person-centred interventions, ultimately improving long-term well-being.

Flexible Organic Radical Cocrystal With 94% Photothermal Conversion Efficiency

ABSTRACT Flexible photothermal materials made of particulate carbon, metal, polymer, or semiconductors often suffer from interfacial incompatibility, leading to cracking and delamination over prolonged use. These limitations make it difficult for flexible composite materials to simultaneously meet the requirements of long‐term interfacial stability and high photothermal performance. Here we circumvented these persistent challenges by using flexible organic crystals, where the absorber is a structurally homogeneous radical cocrystal and strong light absorption is accomplished by charge transfer (CT) between two molecular components. We cocrystallized electron donor perylene (PE) and acceptor naphthalene diimide (NDI) to prepare mechanically flexible, centimeter‐size cocrystals (PE‐NDI), which demonstrate persistent radical characteristics with a spin coherence time of 2.1 µs. Prominent donor–acceptor interaction (−87.7 kJ mol −1 ) facilitates strong light absorption from 200 to 780 nm, while hydrogen bonds are thought to account for the reversible elastic bending. Excitation at 685 nm yields an extraordinarily high photothermal conversion efficiency of 94%. Integration of PE‐NDI in a thermoelectric generator enabled direct solar energy harvesting via a photo‐thermo‐electric conversion sequence, demonstrating the potential of flexible cocrystals for renewable energy harvesting. This work highlights the untapped potential of mechanically compliant organic crystals as flexible, single‐component, lightweight photothermal materials.

Moisture-induced variations in toughness and stress intensity factors of natural and hybrid composites: An experimental–FEM study

Experimental analysis of an enhanced biogas injera baking stove with an inverted conical combustion chamber

tRNA modifications in viral replication

From endotoxin to engineered agonists: A translational strategy to enable TLR4-based immunomodulation in pancreatic cancer.

e14605 Background: Pancreatic ductal adenocarcinoma (PDAC), a lethal malignancy with a dismal 5-year overall survival is highly resistant to immunotherapy. Previously, we established that TLR4 agonism using lipopolysaccharide (LPS) remarkably reduces tumor burden in PDAC by inducing an early inflammatory cytokine surge involving TNF⍺ and IFN𝛾, that promotes cytotoxic CD4⁺ T-cell-mediated antitumor immunity. However, the systemic toxicity of LPS represents a major barrier to clinical translation. Here, we sought to define whether TLR4-agonism mediated anti-tumor effects can be preserved while progressively mitigating toxicity through structural modification of LPS-derived molecules. Methods: KPC pancreatic cancer cells were implanted subcutaneously into syngeneic C57BL/6 mice. Tumor-bearing mice were treated with LPS, Lipid A (TLR4 binding moiety), and structurally modified TLR4 agonists that were generated through bacterial enzymatic combinatorial chemistry, called BECC compounds. Tumor growth was assessed and systemic toxicity was evaluated using murine sepsis scoring and physiologic monitoring. Immune activation was characterized by serum cytokine profiling, flow cytometric analysis of splenic and intratumoral immune populations, and ex vivo CD4⁺ T-cell cytotoxicity assays. Dose-response relationships were assessed where toxicity profiles permitted escalation. Results: As expected, LPS treatment resulted in significant tumor reduction but was associated with marked systemic toxicity. Lipid A failed to reproduce consistent antitumor efficacy in this PDAC model. This is consistent with a skewed Type I interferon (IFN) response, a typical characteristic of vaccine adjuvants, rather than a pro-inflammatory anti-tumor response. Guided by these structure-function observations, BECC compounds were engineered to selectively retain antitumor-relevant immune signaling while eliminating toxicity-associated moieties. Preliminary analyses demonstrate that select BECC compounds (including BECC44 and BECC470) exhibit minimal systemic toxicity and are associated with promising reductions in tumor burden based on endpoint tumor weight measurements. Mechanistic studies are ongoing to determine whether they engage the same immune pathways as defined for LPS. Conclusions: These findings support a structure-guided, iterative approach to reducing the risks associated with TLR4 agonism for cancer immunotherapy. By selectively modifying molecular features, antitumor immune activity may be preserved while progressively reducing systemic toxicity. Next-generation TLR4 agonists such as BECC compounds represent a promising therapeutic strategy for PDAC and warrant further optimization and mechanistic validation.

Real-world clinical outcomes by HER2 expression in locally advanced/metastatic urothelial carcinoma (la/mUC): Results from the global SGNDV-003 retrospective study.

4562 Background: Approximately 50-80% of patients (pts) with la/mUC have tumors with HER2 protein expression. As HER2-directed therapies enter development, a robust understanding of HER2 prevalence and real-world outcomes with standard-of-care (SOC) therapies across HER2 expression subgroups is needed. SGNDV-003 (NCT05902494) is a global retrospective chart review study in which HER2 status was assessed via central lab testing and outcomes were analyzed by HER2 status in pts with la/mUC. Methods: SGNDV-003, conducted 6/2023-7/2025, included pts with la/mUC who received ≥1 prior treatment (tx) (incl. 1 line of platinum-based chemotherapy [chemo]). HER2 status was centrally tested using a UC-specific investigational immunohistochemistry [IHC] and in situ hybridization (ISH) assays. HER2 status was defined as: HER2-positive (IHC3+ or IHC2+/ISH+), HER2-low (IHC2+/ISH- or IHC1+), HER2-expressing (IHC3+, 2+, 1+), and HER2-zero (IHC0). Index line of therapy (LOT) was defined as the first LOT received after platinum-based chemo. Outcomes included real-world objective response rate (rwORR) (per RECIST 1.1 or physician-assessed response) to index LOT, real-world progression-free survival (rwPFS), and overall survival (OS) from start of index LOT. Data was analyzed via descriptive statistics. Results: A total of 353 pts with la/mUC and available HER2 status were analyzed (male, 76%; median age, 70 years). 70% of pts were HER2 expressing (19% HER2-positive, 51% HER2-low); 30% were HER2-zero. Disease characteristics were well balanced by HER2 status. Index LOT tx and real-world outcomes are shown in the Table. Immuno-oncology therapies (IO) and enfortumab vedotin (EV) were the most common index LOTs. For IO, rwORRs were 21% for HER2-expressing and 17% for HER2-zero. For EV mono, rwORRs were 36% (HER2-expressing) and 38% (HER2-zero), respectively. Conclusions: This global study provides a robust estimate of HER2 distribution in la/mUC based on standardized central lab testing, showing high prevalence of HER2 expression. Real-world outcomes with current SOC therapies were broadly consistent across HER2 subgroups, establishing an important benchmark for the clinical development of HER2-directed therapies in this setting. HER2-positive (n=67) HER2-low (n=181) HER2-expressing (n=248) HER2-zero (n=105) Total (n=353) Real-world Outcomes rwORR, n (%)[95% CI] 17 (25.4)[15.5, 37.5] 50 (27.6)[21.3, 34.7] 67 (27.0)[21.6, 33.0] 22 (21.0)[13.6, 30.0] 89 (25.2)[20.8, 30.1] Median rwPFS (95% CI), mo 2.8(2.0, 4.1) 3.7(2.7, 5.1) 3.0(2.7, 4.5) 2.6(2.1, 3.4) 2.9 (2.6, 3.5) Median OS(95% CI), mo 12.2(9.3, 16.5) 11.5(9.5, 13.5) 11.9(10.3, 13.4) 7.7(5.9, 9.9) 10.8(9.1, 12.3) Index LOT, n% IO EV monoChemoOther tx 37 (55)17 (25)10 (15)3 (5) 94 (52)51 (28)24 (13)14 (8) 131 (53)68 (27)34 (14)17 (7) 65 (62)21 (20)12 (11)7 (7) 196 (56)89 (25)46 (13)24 (7)

Association of concurrent COVID-19 infection with in-hospital outcomes among patients hospitalized for head and neck cancer.

e18132 Background: Patients with head and neck cancer (HNC) often have substantial comorbidity and may be particularly vulnerable to adverse outcomes when hospitalized with COVID-19. National data examining inpatient complications, mortality, healthcare utilization, and socioeconomic disparities in this population remain limited. Methods: We conducted a retrospective, survey-weighted analysis of the National Inpatient Sample (2020–2022), identifying adult hospitalizations with a primary diagnosis of HNC. Admissions were stratified by concurrent COVID-19 infection. Demographics, comorbidities, socioeconomic factors, and in-hospital outcomes were compared. Unadjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: An estimated 77,960 hospitalizations for HNC without COVID-19 and 840 with concurrent COVID-19 were identified. Mean age was similar between groups (64.1 vs 64.0 years), and most patients were male. COVID-positive HNC patients were more likely to be insured by Medicaid and to reside in lower-income areas, and had greater comorbidity burden (mean Elixhauser Comorbidity Index 4.83 vs 4.08; p <0.001). Concurrent COVID-19 infection was associated with higher odds of acute kidney injury (OR 3.02, 95% CI 2.31–3.95), sepsis (OR 2.51, 95% CI 1.71–3.69), pneumonia (OR 2.15, 95% CI 1.56–2.95), mechanical ventilation (OR 1.94, 95% CI 1.42–2.66), vasopressor use (OR 2.04, 95% CI 1.28–3.24), and cardiac arrest (OR 2.84, 95% CI 1.41–5.73). In-hospital mortality was higher among COVID-positive admissions (8.9%), with nearly fourfold increased odds of death (OR 3.81, 95% CI 2.88–5.03). COVID-positive hospitalizations also had longer mean length of stay (11.2 vs 6.8 days) and higher mean charges ($157,618 vs $130,717; p <0.001). Conclusions: Among patients hospitalized primarily for HNC, concurrent COVID-19 infection was associated with increased risk of severe in-hospital complications, higher mortality, and greater healthcare utilization, disproportionately affecting socioeconomically disadvantaged patients. In-hospital complications and mortality associated with concurrent COVID-19 in patients hospitalized for head and neck cancer. Outcome Without COVID-19 With COVID-19 Odds Ratio In-hospital mortality 2.51 % 8.93% 3.81 (95% CI 2.88–5.03) Acute kidney Injury 6.98 % 18.45% 3.02 (95% CI 2.31–3.95) Sepsis 3.23% 7.74% 2.51 (95% CI 1.71–3.69) Pneumonia 4.98% 10.12% 2.15 (95% CI 1.56–2.95) Mechanical Ventilation 6.16% 11.31% 1.94 (95% CI 1.42–2.66) Vasopressor Use 1.78% 3.57% 2.04 (95% CI 1.28–3.24) Cardiac Arrest 0.85% 2.38% 2.84 (95% CI 1.41–5.73)

ASCENT-03: Efficacy by biomarker subgroup with sacituzumab govitecan (SG) vs chemotherapy (chemo) in participants (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors (PD-[L]1i).

1014 Background: SG demonstrated significant and clinically meaningful progression-free survival (PFS) improvement vs chemo in pts with previously untreated, locally advanced unresectable or metastatic TNBC who were not candidates for PD-(L)1i in ASCENT-03 (NCT05382299). We report preplanned exploratory efficacy analyses in ASCENT-03 by Trop-2 expression, BRCA status, and HER2 expression. Methods: 588 pts randomized 1:1 to SG or chemo (taxane or gemcitabine + carboplatin). Trop-2 expression was measured by immunohistochemistry (IHC), tumor BRCA (tBRCA) status by whole exome sequencing, and HER2 expression by in situ hybridization (ISH) and IHC, all in centrally tested tumor samples (fresh or archival; 43% from metastatic sites). Pts were subgrouped by Trop-2 expression quartile, tBRCA wild-type (WT) or mutant (mut; mut in BRCA1, BRCA2, or both) status, and HER2 status (IHC 0 vs Low [IHC 1+ or IHC 2+/ISH-]). Biomarker status was analyzed to determine association with PFS by blinded independent central review (BICR). Other efficacy outcomes by biomarker status will be presented. Results: Median Trop-2 H-score: 240; H-scores by quartile (Q): Q1 0-184, Q2 185-239, Q3 240-283, Q4 284-300. Trop-2 expression was available in 499 pts. PFS by BICR was longer with SG vs chemo in all Trop-2 expression quartiles (Table). Hazard ratio (HR; 95% confidence interval [CI]) was 0.54 (0.35-0.84) in Q1, 0.62 (0.40-0.97) in Q2, 0.84 (0.54-1.31) in Q3, and 0.60 (0.38-0.95) in Q4. tBRCA status was available in 423 pts; proportion of pts with tBRCA mutations was comparable between treatment groups (~18%). PFS was longer with SG vs chemo in tBRCA WT and mut subgroups, with HR (95% CI) 0.70 (0.54-0.92) in tBRCA WT and 0.59 (0.32-1.09) in tBRCA mut. HER2 status was available in 551 pts; PFS was longer with SG vs chemo in both HER2 subgroups. HR was 0.63 (0.46-0.85) in the IHC 0 subgroup and 0.74 (0.55-1.01) in the HER2 Low subgroup. Conclusions: PFS was longer with SG vs chemo across all Trop-2 categories, tBRCA genotypes, and HER2 subgroups. These results reinforce the significant, clinically meaningful benefit of SG as first-line treatment for pts in this population across multiple biomarker subgroups. Clinical trial information: NCT05382299 . Efficacy, BICR N Median PFS (95% CI), months Biomarker Subgroup SG Chemo SG Chemo HR (95% CI) Trop-2(n = 499) Q1 68 55 8.5(5.6-12.7) 5.5(4.2-8.1) 0.54(0.35-0.84) Q2 60 62 8.3(5.6-12.4) 6.8(4.2-9.0) 0.62(0.40-0.97) Q3 50 74 9.7(7.6-11.3) 7.0(5.3-8.5) 0.84(0.54-1.31) Q4 74 56 9.9(6.9-NR) 8.1(4.4-8.5) 0.60(0.38-0.95) tBRCA(n = 423) WT 177 169 8.8(7.2-9.9) 6.9(5.4-8.3) 0.70(0.54-0.92) Mut 40 37 12.7(7.2-18.7) 8.3(5.6-11.2) 0.59(0.32-1.09) HER2(n = 551) IHC 0 115 138 8.3(6.9-10.3) 5.6(4.3-7.0) 0.63(0.46-0.85) Low 159 139 9.8(8.3-12.4) 8.3(5.7-9.7) 0.74(0.55-1.01)

Temporal trends and demographic disparities in cardiovascular disease (CVD) and hepatocellular carcinoma (HCC)–related mortality in the United States, 1999–2020: CDC WONDER Analysis.

e16360 Background: Hepatocellular Carcinoma (HCC) is the fifth most common cause of cancer worldwide. Five-year survival of HCC is 18% and second to pancreatic cancer. Cardiovascular disease (CVD) is increasingly recognized as a major competing cause of death in patients with liver disease, but national data on long-term trends and demographic disparities in CVD-associated mortality among the HCC population are limited. This study aims to analyze demographic disparities and temporal trends among adults aged 25 and older from 1999 to 2020. Methods: Data from CDC WONDER was extracted using ICD-10 codes C22 (Malignant neoplasm of liver and intrahepatic bile ducts) and I00-I99 (Diseases of the circulatory system) from 1999 to 2020 to obtain age-adjusted mortality rates (AAMR) per million stratified by year, gender, race, state, urban-rural status, census region, and place of death (POD). Joint Point regression analysis was performed to calculate annual percent change (APC) and average annual percent change (AAPC). Results: About 98,777 deaths were reported during the study period. Overall, AAMR increased from 15.461 in 1999 to 25.79 in 2020, 2.36% per year (AAPC 2.36%; 95% CI 2.22–2.50; P < 0.000001). AAMR for males (30.38 vs 12.22) was higher than for females, with a trend increase of rate in males (AAPC: 2.46% per year (95% CI, 2.28–2.63)) compared to females (AAPC: 1.86% per year (95% CI, 1.57–2.14)). Non-Hispanic (NH) Asian or Pacific Islander had the highest AAMR (40.4), followed closely by Hispanic White (39.2), NH American Indian or Alaska Native (29.1), NH Black or African American (27.83), Hispanic Asian or Pacific Islander (20.2), and lastly NH White (16.6). Among the regions, the West had the highest AAMR (27.9), followed by the Northeast (22.264), the South (18.534), and lastly the Midwest (16.051). Urban areas had higher AAMR (20.872) than rural areas (18.03). California had the highest AAMR of 39.5. The majority of deaths occurred at the decedents' homes (39.5%), followed by inpatient medical facilities (32.7%). Conclusions: Mortality rates have been increasing steadily from 1999 to 2020 in HCC patients with CVD, with marked disparities among sex, race, region, urban-rural, state, and place of death, with the highest burdens among NH Asian/Pacific Islander and Hispanic populations, residents of the West, and urban areas. These findings underscore the need for targeted research and prevention strategies in high-risk demographic groups to mitigate the growing burden.

Real-world treatment patterns, genomic profiling access, and survival outcomes in advanced lung adenocarcinoma: A retrospective cohort analysis from a resource-limited setting.

e20722 Background: Real-world management of advanced NSCLC in LMICs is constrained by low biomarker testing rates(PD-L1, NGS), later-line systemic chemotherapy dominance over unaffordable 2nd-generation TKIs and absent novel targeted agents. This retrospective analysis evaluates outcomes with targeted therapy utilization in an Indian real-world cohort. Methods: We performed a retrospective analysis of 200 consecutive patients diagnosed with stage III/IV lung adenocarcinoma between 2021 and 2025. Data were extracted from medical records, including demographic details, smoking history, molecular testing results (EGFR, ALK, ROS1, KRAS, TP53, others), treatment modalities (chemotherapy, targeted therapy, immunotherapy), progression status, and survival. Overall survival (OS) was defined from the date of diagnosis to the date of death or last follow-up (censored). Kaplan–Meier method was used to estimate survival curves, and the log-rank test was applied to compare survival between groups. Multivariable Cox proportional hazards models were used to identify predictors of survival. Results: Median age was 55 years, with 50.5% males and 54.8% non-smokers. Molecular profiling was performed in 76% patients; actionable mutations were identified in 65%, including EGFR-35%, ALK-15%, ROS1-6%, and others. Only 56% of mutation-positive patients received targeted therapy, 82% receiving chemotherapy only or in later lines - predominantly pemetrexed and carboplatin and immunotherapy in < 5% patients. Median OS for the entire cohort was 12.0 months (95% CI 9.8–14.2). Patients receiving targeted therapy had significantly longer median OS compared to those on chemotherapy alone (24.0 vs. 8.0 months, p < 0.001, HR 0.42, 95% CI 0.28–0.63). In Subgroup analysis : EGFR+ median OS 28 months and ALK+ 22 months. In multivariable analysis, independent predictors of improved OS included receipt of targeted therapy (HR 0.45, 95% CI 0.29–0.70). Lack of molecular testing was associated with worse OS (HR 1.85, 95% CI 1.22–2.80). Conclusions: In this real-world cohort from a resource-limited setting, access to molecular testing and targeted therapy was suboptimal but strongly correlated with improved survival outcomes. Financial barriers preventing the translation of biomarker discovery into treatment delivery, directly impacting survival. These findings underscore the urgent need for health system interventions to improve access to precision medicine for patients with advanced lung cancer worldwide.

Final analysis of the biomarker-directed, randomized, phase 2 KEYNOTE-495/KeyImPaCT study of pembrolizumab (P)–based combination therapy for non–small cell lung cancer (NSCLC).

8584 Background: KEYNOTE-495/KeyImPaCT (NCT03516981) evaluated 3 P-based regimens in participants (pts) with advanced NSCLC across 4 prospectively defined biomarker subgroups based on T-cell–inflamed gene expression profile (Tcell inf GEP) and tumor mutational burden (TMB). In interim analysis, ORR with P + lenvatinib (L) in the Tcell inf GEP non-low TMB high subgroup met the prespecified efficacy threshold. We report final analysis results. Methods: Pts with previously untreated NSCLC were assessed for Tcell inf GEP (non-low, ≥−0.16; low, <−0.16) and TMB (high, ≥5 mut/Mb; non-high, <5 mut/Mb; ≈175 mut/exome by WES and 10 mut/Mb on FoundationOne CDx). Pts were assigned to 1 of 4 subgroups (Tcell inf GEP low TMB non-high , Tcell inf GEP low TMB high , Tcell inf GEP non-low TMB non-high , and Tcell inf GEP non-low TMB high ) and adaptively randomized 1:1:1 to P (200 mg IV Q3W) + either L (20 mg PO QD), quavonlimab (Q; 25 mg IV Q6W), or favezelimab (F; 200 mg or 800 mg IV Q3W). The primary end point was ORR per RECIST v1.1 by investigator. Secondary end points included PFS, OS, and safety. Data cutoff: July 30, 2025. Results: 243 pts were treated (P + L, 80; P + Q, 82; P + F 200 mg, 30; P + F 800 mg, 51). Median follow-up was 66.5 mo (range, 43.0-81.2). The Tcell inf GEP non-low TMB non-high subgroup treated with P + L met the prespecified efficacy threshold (≥95% posterior probability of true ORR >20%); PFS and OS were generally consistent with anticipated results among biomarker-defined subgroups (Table). Safety profile of each combination was consistent with the known profiles of each therapy. Conclusions: With longer follow-up, OS benefit was comparable across the 4 biomarker subgroups for the 3 combination therapies, with no new safety signals. These data continue to show the feasibility of prospective biomarker assessment to evaluate P-based therapies in advanced NSCLC. Clinical trial information: NCT03516981 . Tcell inf GEP low TMB non-high Tcell inf GEP low TMB high Tcell inf GEP non-low TMB non-high Tcell inf GEP non-low TMB high ORR, % (95% CI)  P + LP + QP + F 200 mgP + F 800 mg 12.0 (2.5-31.2)11.5 (2.4-30.2)0.0 (0.0-28.5)27.3 (6.0-61.0) 33.3 (9.9-65.1)30.8 (9.1-61.4)33.3 (4.3-77.7)13.6 (2.9-34.9) 40.9 (20.7-63.6)13.6 (2.9-34.9)25.0 (3.2-65.1)- 57.1 (34.0-78.2)52.4 (29.8-74.3)60.0 (14.7-94.7)50.0 (26.0-74.0) Median (95% CI) PFS, mo  P + LP + QP + F 200 mgP+ F 800 mg 5.4 (2.3-8.8)2.8 (2.0-6.0)2.1 (1.9-2.1)4.2 (1.8-12.2) 13.8 (1.5-19.4)3.9 (1.9-17.3)8.1 (1.7-NR)3.5 (2.0-8.2) 8.2 (4.2-19.7)6.1 (2.1-12.8)2.1 (0.9-6.5)- 17.8 (6.0-20.7)17.0 (9.3-29.1)6.3 (0.4-NR)20.2 (6.1-NR) Median ( OS, mo  P + LP + QP + F 200 mgP + F 800 mg 16.0 (5.4-20.2)13.3 (8.4-20.0)8.6 (3.8-35.4)18.6 (3.4-41.2) 16.9 (3.8-33.2)20.1 (7.7-NR)20.8 (1.7-NR)11.1 (5.2-19.6) 22.5 (12.0-41.3)23.7 (7.9-43.1)12.6 (0.9-25.4)- 22.7 (16.9-56.0)51.6 (17.6-NR)NR (13.5-NR)NR (13.0-NR) -, no pts enrolled. NR = not reached.

Post-hoc efficacy and biomarker analysis of elraglusib plus gemcitabine/nab-paclitaxel versus chemotherapy alone in metastatic pancreatic ductal adenocarcinoma.

4213 Background: Elraglusib (9-ING-41), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has multimodal antitumor activity. In the international, open-label, randomized phase 2 1801 Part 3B study, elraglusib plus gemcitabine/nab-paclitaxel (GnP) was evaluated in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC), with patients randomized 2:1 to weekly elraglusib/GnP or GnP alone. Primary endpoints were median overall survival (mOS) and 1-year survival. The GnP control arm demonstrated shorter mOS than contemporary randomized trials (7.2 months vs 9.2 months in NAPOLI-3 and 9.7 months in PASS-01), driven by higher early mortality (0–2 months: 23.1% vs 10.1% in NAPOLI-3). Given balanced randomization, similar early mortality was inferred in the elraglusib/GnP arm, prompting post-hoc analyses to contextualize efficacy and identify factors associated with early death. Methods: Efficacy and safety were summarized descriptively. Time-to-event endpoints were analyzed using Kaplan–Meier estimates, log-rank testing, and Cox proportional hazards models. Response rates were compared using the Cochran–Mantel–Haenszel test. Post-hoc subgroup, sensitivity, and machine-learning–based multivariate analyses explored clinical, demographic, and biomarker correlates of survival and early mortality. Results: In the full randomized population (elraglusib/GnP n=155; GnP n=78), elraglusib/GnP improved mOS by 2.9 months versus GnP (10.1 vs 7.2 months; HR 0.62; 95% CI 0.46–0.84; p=0.01), with 1-year survival rates of 44.1% versus 22.3%. Among patients receiving ≥1 full treatment cycle, mOS was 12.5 months with elraglusib/GnP and 8.5 months with GnP, comparable to contemporary registrational trials. Across multiple post-hoc sensitivity analyses—including evaluable patients, those matched to NAPOLI-3 baseline tumor burden, patients treated in the EU (early mortality 4%), and those achieving ≥20% CA19-9 decline within the first 1–2 cycles—elraglusib/GnP consistently demonstrated a ≥4-month OS advantage. Early death was associated with low baseline albumin (<3 g/dL), high CA19-9 (>800 U/mL), high tumor burden, and KRAS, TP53, and CDKN2A co-mutations. Conclusions: The elevated early mortality in the GnP control arm reflects enrollment of a heterogeneous, real-world mPDAC population with less restrictive eligibility than recent registrational trials. Post-hoc analyses identify key clinical and molecular drivers of early death and confirm a consistent survival benefit with elraglusib/GnP. These hypothesis-generating findings directly inform eligibility criteria, stratification, and endpoint assumptions for the planned phase 3 trial. Clinical trial information: NCT03678883 .

Safety and efficacy of pembrolizumab plus lenvatinib as first-line therapy in non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

e20634 Background: Pembrolizumab, an anti-PD-1 antibody, and Lenvatinib, a multi-kinase inhibitor, were identified as potentially effective treatment agents for various malignancies, including non-small cell lung cancer (NSCLC). Prior research indicated that the combination of these two drugs may significantly enhance survival outcomes compared to conventional treatments. Nevertheless, the safety and efficacy of Pembrolizumab plus Lenvatinib as first-line treatment for NSCLC remain uncertain. This study aims to evaluate the therapeutic effects and possible risks of this combination therapy in patients with NSCLC by assessing outcomes, including overall survival, progression-free survival, and adverse events. Methods: Following PRISMA guidelines and registration with PROSPERO, databases including PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched from inception to January 2026 for studies evaluating the efficacy and safety of Pembrolizumab plus Lenvatinib in patients with NSCLC undergoing first-line therapy. Data were analyzed using RevMan version 5.4 with a random-effects model to estimate pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals. A p-value < 0.05 was considered statistically significant. Results: Six studies (n = 2,164) assessed the efficacy and safety of Pembrolizumab plus Lenvatinib in patients with NSCLC receiving first-line therapy. The combination treatment significantly reduced the risk of progression by 15% (HR 0.85; 95% CI 0.76–0.95; p = 0.005), though no significant difference in overall survival was observed (HR 1.05; 95% CI 0.93–1.18; p = 0.42). Pembrolizumab plus Lenvatinib also demonstrated a 30% higher overall response rate (RR 1.30; 95% CI 1.08–1.57; p = 0.005), with moderate heterogeneity (I² = 49%). However, this treatment was associated with an increased risk of grade 3-5 treatment-related adverse events (TRAEs) (RR 1.41; I² = 90%) and a higher risk of TRAEs, which leads to discontinuation (RR 1.81) and death (RR 2.39). Conclusions: Pembrolizumab plus Lenvatinib as first-line treatment in patients with NSCLC showed potentially effective therapeutic benefits by significantly lowering the risk of progression and increasing the overall response rate. Conversely, the combination is correlated with an increased risk of TRAEs of grade 3-5, accompanied by a higher probability of TRAEs leading to discontinuation and death. Future studies with large sample sizes are needed to validate these results and provide insight of risk-to-benefit ratio of this combined therapy

Real-world distribution of antibody–drug conjugate (ADC)–associated adverse events (AEs) in breast cancer patients: An EPIC Cosmos database analysis.

e13079 Background: AEs among ADC-treated breast cancer patients (BCPs) are associated with targeted antigens (TROP2, HER2) on normal tissue, payload direct and bystander effects, and ADCC-mediated cytotoxicity. Here we define real-world reports of incidence, distribution, and consequences of ADC-AEs and assess payload or antigen target roles in AE risk. Methods: ADC treated BCPs between 11/22 and 11/25 were identified in the EPIC-COSMOS dataset (n 2,304,438 in 310 health systems). ADC-treated BCPs were included who were prescribed ADCs within 3 months of BC diagnosis (dx) and had a BC dx documented as an encounter dx, admitting dx, billed final dx, billed admitting dx, billed charge-associated dx, or an active dx on the problem list in the query date range. AEs were assigned if they occurred within 6 months of ADC initiation. Results: Of 32,795 BCPs identified in the dataset, 28,040 had treatment-associated AEs (85.5%). HER2 was the dominant antigen target (75%) followed by TROP2 (23%). Most common payloads were emtasine (EM), deruxtecan (DER), and govitecan (GOV). ADCs, not typically used in BC were reported in 1% of cases. Across all ADCs, 76% of patients were aged 40y-75y. No difference in ADC use or frequency was noted as a function of either race or insurance coverage (White n 20,731[58.3%], AEs [58.8%]; Black or African American n 5,373 [15.1%], AEs 15.5%; Other 4,277 [12%], AEs 11.9%; Asian 1,424 [4%], AEs 3.9%). Of patients who received ADCs, AE frequency regardless of race was similar (range 76%-83.7%). Insurance type did not impact AE frequency (Commercial 40.5% of ADC patients; Medicare 37%; AE range [82.3%-85.8%]). Differences in the frequency and distribution of anemia, diarrhea, nausea, anorexia, neutropenia/febrile neutropenia (N/FN) were associated with payload (EM vs DER) not antibody target, but oral mucositis risk was more likely with TROP2- vs HER2-targeted ADC with similar payloads (Table 1). N/FN was more common in ADCs with DER (FN 14.8%) or GOV (29.8%) payloads vs EM (6.7%). Pneumonitis was rare ( < 1%). Of patients with AEs, hospitalizations varied by payload: EM 22%, GOV 57%, DER 47%, as did ICU admissions of ≥ 4 days (EM 14%, GOV 44%, DER 34%). Conclusions: RWD reported AEs are common among ADC-treated BC patients targeting HER2 or TROP2. AE distribution and outcome impact appear to be most impacted by ADC payload. Selected Adverse Event Rates Across Antibody–Drug Conjugates (N = 33,311). ADC Total Patients Anemia Diarrhea Fatigue Nausea Vomiting Alopecia Constipation Anorexia Oral Mucositis Abdominal Pain ado-trastuzumab emtansine 10,269 15.2% 7.3% 15.4% 13.1% 0.9% 1.0% 7.6% 2.7% 0.7% 5.0% datopotamab deruxtecan 259 16.2% 5.4% 9.7% 14.3% - - 10.0% 7.0% 8.5% 5.4% fam-trastuzumab deruxtecn 14,700 23.4% 15.0% 17.7% 23.8% 2.2% 1.6% 11.0% 7.7% 1.8% 7.4% sacituzumab govitecan 7,514 26.7% 18.1% 16.7% 21.0% 1.9% 1.2% 10.5% 8.4% 8.4% 8.7%

AI-powered social media listening of oncologist conversations at ASCO 2025.

9045 Background: Major oncology congresses generate extensive expert-driven discussion on social media around clinical trial data. However, standardized methods to systematically capture, contextualize, and evaluate these conversations remain limited. LARVOL CLIN is an AI-powered platform that analyzes oncology-focused discussions on X (formerly Twitter), enabling systematic evaluation of clinical trial discourse through assessment of trial-level activity, oncologist sentiment, and engagement. Methods: This observational, descriptive analysis evaluated oncology-related posts on X associated with ASCO 2025 (from Apr 23, 2024, to Jan 14, 2025). Posts were identified using predefined conference- and trial-specific keywords and underwent manual validation to confirm relevance to oncology clinical trials. Text-based sentiment analysis was conducted exclusively on posts from oncologists, while trial-related images and polls from both oncologist and non-oncologist X accounts were reviewed for relevance. Validated content was analyzed using oncology-trained large language models, based on ChatGPT 5.1, to interpret clinical context, including efficacy, safety, endpoint status, and potential practice relevance. Sentiment was categorized as negative, neutral, positive, or strongly positive. Results: A total of 4,621 oncology clinical trial–related X posts from 651 digitally active oncologists were analyzed for ASCO 2025. Sentiment profiles varied across trials (Table 1). Some studies demonstrated a higher proportion of positive or strongly positive sentiment while others were characterized primarily by neutral assessments reflecting cautious clinical interpretation. Neutral sentiment constituted a substantial share of oncologist posts, often reflecting data interpretation, contextual discussion, or pending clinical relevance. Negative sentiment was typically associated with limited efficacy signals, safety considerations, or unmet expectations. Conclusions: This ASCO 2025 observational study demonstrates that AI-driven social listening can systematically capture, contextualize, and quantify expert oncology discourse surrounding clinical trial presentations. LARVOL CLIN enables real-time assessment of oncologist sentiment supporting medical affairs, outcomes research, and strategic communication. Digital oncologist activity for selected ASCO 2025 trials. Trial (Abstract ID) Views (K) Not Rated Negative Neutral Positive Strongly Positive Total X Posts PACIFIC15 (8516) 798 47 10 14 25 14 110 DESTINY-Breast09 (LBA1008) 477 32 4 14 24 34 108 SERENA-6 (LBA4) 358 36 9 15 39 26 125 ASCENT-04 (LBA109) 355 22 2 5 25 34 88 ATOMIC (LBA1) 290 25 4 8 27 40 104 LARVOL CLIN represents cumulative views across all X posts for each trial. Sentiment categories reflect AI-generated classification of oncologist X posts.