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Neoadjuvant intravenous biosimilar pertuzumab and trastuzumab versus subcutaneous pertuzumab/trastuzumab/hyaluronidase (Phesgo) in HER2-positive breast cancer: A real-world comparative study.

e12604 Background: Dual HER2 blockade with pertuzumab and trastuzumab combined with chemotherapy is the standard neoadjuvant treatment for HER2-positive breast cancer. In low- and middle-income countries, biosimilar pertuzumab and trastuzumab are increasingly used due to improved affordability. Phesgo, a fixed-dose subcutaneous formulation of pertuzumab and trastuzumab, offers logistical convenience. Comparative real-world data evaluating neoadjuvant outcomes between biosimilar-based intravenous dual HER2 blockade and Phesgo are limited. Methods: This retrospective observational study included patients with HER2-positive breast cancer who received neoadjuvant chemotherapy and dual HER2 blockade using either intravenous biosimilar Pertuzumab with Trastuzumab or subcutaneous fixed dose combination of Pertuzumab/Trastuzumab/Hyaluronidase i.e, Phesgo (Roche) from 01.01.2024 to 20.01.2026. Baseline demographic and clinicopathological characteristics, neoadjuvant regimens, surgical outcomes, and pathological response were analyzed. Pathological complete response (pCR) was defined as ypT0N0 or ypTisN0 among patients who underwent surgery. Results: A total of 219 patients were analyzed, of which 149 (68%) received biosimilar pertuzumab/trastuzumab and 70 (32%) received Phesgo. Median age was comparable between the groups (52 vs 53 years). Hormone receptor–positive disease was seen in 45.7% and 51.4% of patients, respectively. The majority of patients in both cohorts had T1–T2 tumors (62.4% vs 62.9%), while node-positive disease was more frequently observed in the Phesgo cohort (67.8% vs 77.1%). Neoadjuvant chemotherapy was administered in 96% of patients in both cohorts, most commonly TCHP regimen. At the time of analysis, neoadjuvant treatment was ongoing in 31 of 149 patients (20.8%) in the biosimilar group compared with 3 of 70 patients (4.3%) in the Phesgo group. Surgery was completed in 65.8% of the biosimilar group and 82.8% of the Phesgo group, with comparable breast-conserving surgery rates (33.7% vs 34.5%). Among patients with available surgical pathology data (n = 92 vs n = 56), pCR rates were similar between cohorts (ypT0N0: 64.1% vs 64.3%; ypTisN0: 2.17% vs 1.8%). No significant adverse events reported other than diarrhoea. None of them had treatment discontinuation due to cardiac toxicity. Conclusions: Neoadjuvant chemotherapy combined with biosimilar intravenous pertuzumab and trastuzumab achieved pathological response and surgical outcomes comparable to Phesgo in patients with HER2-positive breast cancer. Clinical implications: These findings support biosimilar-based dual HER2 blockade as an effective and affordable neoadjuvant strategy, particularly relevant for improving access to standard-of-care therapy in resource-constrained settings.

The effect of automated quantitative evaluation of lesion response heterogeneity in patients with metastatic neuroendocrine tumors.

e16318 Background: Neuroendocrine tumors (NET) are a biologically diverse set of neoplasms that vary in malignant potential. The wide spectrum of disease tempos and the long course require timely clinical judgement for good long-term outcomes. Clinical decision making is critically dependent on imaging results; however, the lack of detail and variation in reports can make the process inconsistent. Automated quantitative analysis of change in every lesion over the course of treatment can contribute to the standardization of therapeutic decisions by providing more precise calculations of disease progression. Methods: A retrospective analysis of fifty-one patients from a high-volume neuroendocrine practice was completed to evaluate the clinical utility of automated lesion quantification from DOTATATE PET/CT PET scans. The automated analysis provided total standardized uptake values (total, max and mean) for the total disease and each lesion, lesion volume, and a 3-D spatial map showing the location of each lesion. PET/CT reports from the radiologist were assessed for the presence of both qualitative and quantitative information. Clinical decisions based on the imaging automated analysis and radiology report were correlated. Results: Fifty-one consecutive patients with metastatic NET were analyzed (small intestine/midgut: 42, pancreatic: 6, rectal: 2, appendiceal 1). Radiologists mentioned the total number of lesions in 12%, lesions size change in 58%, and clear overall response in 56% of the reports. The automated quantitation gave a Total SUV range from 0 – 23088 and PET Volume 0 – 899 cm3. From these values, we were able to calculate volume disease tempo (change in PET volume/time) which ranged from –992 to 281 cm3/year and SUV disease tempo (change in total SUV/time) which ranged from –15135 to 6760. Patients who underwent surgery/procedure had the largest decrease in quantitative parameters. Patients with volume disease tempo > 25 cm3/year all continued with surveillance. Patients with > 25 cm3/year underwent treatment change. One patient with metastatic small intestinal NET had a 144% increase in total SUV and was administered 177Lu-DOTATATE therapy. After the completion of treatment, the total SUV decreased by 5%. Conclusions: Management of patients with NET requires detailed and timely data, yet it is infeasible for radiologists to provide such data for each lesion. Automated quantitative PET analysis provided comprehensive, standardized data for change in each lesion that proved clinically impactful for decisions to continue or change therapies.

A systems-level omics and hallmark–based analysis of pancreatic cancer for the identification of potential multi-target drugs.

e16441 Background: Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options. Advances in omics technologies enable comprehensive characterization of molecular alterations, while the cancer hallmarks framework provides a biologically informed basis for identifying potential therapeutic targets. Methods: We collected the following data for pancreatic cancer: transcriptomic data from The Cancer Genome Atlas (TCGA), proteomic data from the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium, survival data from HPA and TCGA, and genetic alteration from the Genomic Data Commons Data. We also collected the frequencies of Single Nucleotide Polymorphism (SNP) and copy number variation (CNV). Next, curated contributions of each omics to ten cancer hallmarks (e.g. self-sufficiency in growth) were scored, combining omics layer and their contribution to each hallmark, yielding cumulative scores that were combined multiplicatively for gene prioritization. Prioritized genes were filtered using curated lists of druggable genes from the Human Protein Atlas and the Drug–Gene Interaction Database. Potential therapeutic compounds targeting these genes were then identified using Enrichr with the MAGMA drug database. Results: Survival and transcriptomics data, proteomic data, and CNV/SNP data were collected from 176, 235, and 420 pancreatic cancer patients, respectively. TP53, COL17A1, S100P, PLA2G1B, and CLPS showed the highest omics scores, while MAP2K1, KRAS, AKT1, TP53, and HRAS exhibited the highest genetic alteration scores. Following multiplicative integration of omics and hallmark scores and evaluation of therapeutic target candidacy, TP53, KRAS, MET, RAC1, PIK3CB, ERBB2, CCND1, and FAS emerged as the top-ranked genes. Interestingly, a phase three trial for a new drug targeting RAS in patients with pancreatic cancer is in progress. The results of Enrichment analysis with the top 25 genes are listed in Table 1. Conclusions: This multi-omics and hallmark-directed analysis identifies key potential therapeutic targets in pancreatic cancer, highlighting potential utility of biologically-informed multi-target strategies in new drug discovery. Top-scoring therapeutic targets identified in pancreatic cancer and their potential interacting compounds. Name Combined Score Affected Genes CDK Inhibitor 27481 CCND1;CDKN2A;ERBB2;KRAS;ESR1;TP53 Abemaciclib 27481 CCND1;CDKN2A;ERBB2;KRAS;ESR1;TP53 Osimertinib 25687 ERBB2;KRAS;MET Crizotinib 23266 NPM1;SMAD4;CDKN2A;ERBB2;KRAS;TP53;MET ALK Inhibitors 22887 NPM1;SMAD4;CDKN2A;MET Alectinib 22887 NPM1;SMAD4;CDKN2A;MET Vesnarinone 11950 FAS;TP53;THBS1 Olaparib 7691 MYC;ERBB2;KRAS;ESR1;TP53;MET Venetoclax 7243 NPM1;BCL2;KRAS;TP53 BCL Inhibitor 7243 NPM1;BCL2;KRAS;TP53

Omitting postoperative radiotherapy after pathologic complete response to neoadjuvant immunochemotherapy for patients with locally advanced head and neck squamous cell carcinoma: Survival and patient-reported outcomes.

6105 Background: Neoadjuvant immunochemotherapy (NICT) results in high pathologic response rates in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). However, whether it is safe to omit postoperative radiotherapy (PORT) for patients who achieved pathologic complete response (pCR) after NICT and surgery remains unclear. We assessed the survival and patient-reported outcomes (PROs) for LA-HNSCC patients who achieved pCR to NICT. Methods: This retrospective cohort study included LA-HNSCC patients who achieved pCR to NICT between July 2019 and June 2025. Patients were categorized into two groups based on whether they received PORT. Propensity score matching (PSM) was performed to minimize confounding and balance baseline characteristics. Kaplan-Meier survival analysis was performed to estimate local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS). EORTC QLQ-C30 and EORTC QLQ-HN35 questionnaires before NICT, preoperatively, and at month 1, 3, and 12 postoperatively were collected. Least-squares mean (LS mean) changes from baseline were estimated using linear mixed-effects models for repeated measures (group, time, and group×time), adjusting for baseline scores. Results: A total of 236 HNSCC patients who achieved pCR after NICT and surgery were included (non-PORT, n = 98; PORT, n = 138). After 1:1 PSM to balance baseline characteristics, 164 patients (82 matched pairs) with comparable baseline characteristics were analyzed. With a median follow-up of 31.67 months (95% CI, 29.57-35.35), survival analysis showed no significant differences between the non-PORT and PORT groups in 2-year LRFS, LRRFS, DMFS or OS (all p > 0.05). Longitudinal EORTC QLQ-C30 global health/QOL analyses showed poorer recovery in the PORT group. PORT was associated with significantly greater postoperative QOL decline at 1 and 3 months postoperatively, with a persistent deficit at 12 months , while non-PORT improved above baseline by 12 months whereas PORT remained slightly reduced. On the EORTC QLQ-HN35, PORT was associated with persistently higher symptom burden, peaking at 3 months postoperatively and remaining elevated up to 1 year compared with non-PORT, suggesting potential QOL benefits of omitting PORT in pCR patients. Conclusions: In this propensity score-matched cohort of LA-HNSCC patients achieving pCR after NICT and surgery, omitting PORT was associated with comparable 2-year disease control and survival but better recovery of multidimensional QOL and lower symptom burden on head and neck-specific PROs. These findings favor omission of PORT for this patient population, while prospective validation and longer follow-up are warranted.

Prevention of paclitaxel-induced peripheral neuropathy using limb cryotherapy: Evidence from a resource-constrained setting.

e12690 Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a common, dose-limiting toxicity that significantly impacts quality of life and treatment adherence, particularly with weekly paclitaxel regimens. Currently, no validated preventive strategy exists. Regional limb cryotherapy may reduce drug delivery to peripheral nerves through transient vasoconstriction, thereby mitigating neurotoxicity. We prospectively evaluated the efficacy of limb cryotherapy in preventing PIPN. Methods: This prospective, self-controlled study enrolled 30 patients receiving weekly paclitaxel (80 mg/m² for 12 weeks) for breast cancer. Cryotherapy using pre-cooled gel mittens and socks was applied unilaterally (intervention side) for 15 minutes before, during, and 15 minutes after each paclitaxel infusion; the contralateral limb served as control. Neuropathy assessments were performed at baseline, week 6, and week 12 using objective neurological tests (vibration sense, monofilament testing, thermo-sensory assessment, and manipulative dexterity) and patient-reported outcomes using the EORTC QLQ-CIPN20 questionnaire. Comparisons between intervention and control sides were analyzed using the Wilcoxon signed-rank test. Results: All patients completed planned chemotherapy without cryotherapy-related discontinuation. At week 12, the cryotherapy-treated limbs demonstrated significantly lower neuropathy burden compared with control limbs. Median EORTC QLQ-CIPN20 scores were significantly lower on the intervention side (27.0 vs 29.5; p < 0.001), indicating better quality of life. Preservation of vibration sense, monofilament sensation, thermo-sensory function, and manipulative dexterity was significantly greater in cryotherapy-treated limbs (p ≤ 0.025 for key sensory endpoints). No significant motor deficits were observed in either arm. Conclusions: Limb cryotherapy significantly reduced the severity of paclitaxel-induced peripheral neuropathy and preserved quality of life in this prospective self-controlled study. This low-cost, well-tolerated intervention may represent a feasible preventive strategy for PIPN, particularly in resource-constrained settings. Larger randomized trials are warranted to confirm these findings and define its role in routine clinical practice. Keywords Paclitaxel, chemotherapy-induced peripheral neuropathy, cryotherapy, quality of life, supportive care.

An observational study to investigate the effectiveness and safety of niraparib maintenance therapy after frontline chemotherapy for Taiwanese patients with advanced ovarian cancer: Interim results.

e17546 Background: The phase 3 PRIMA trial demonstrated that first-line maintenance therapy (1LMT) with niraparib significantly prolonged progression-free survival (PFS) in patients (pts) with newly diagnosed advanced ovarian cancer (OC), regardless of homologous recombination deficiency (HRD) or BRCA mutation status. However, the trial population was restricted to non-Asian pts at high risk of recurrence, limiting its generalizability. The real-world evidence on niraparib 1LMT remains limited. This first multicenter study of niraparib 1LMT in Taiwan aims to evaluate its real-world effectiveness and safety as 1LMT following frontline platinum-based chemotherapy (1LCT) in pts with advanced OC. Methods: This multicenter, ambispective, observational study enrolled pts with newly diagnosed FIGO stage III–IV epithelial OC who achieved complete response (CR) or partial response (PR) to 1LCT following either primary or interval debulking surgery, irrespective of residual disease status. Eligible pts initiated niraparib 1LMT on or after January 1, 2022. The primary endpoint was clinical effectiveness, including PFS and related outcomes, with subgroup analyses conducted by BRCA and HRD status. The observation period lasted up to 3.5 years from the first dose of niraparib. Interim analyses were conducted with a data cut-off of June 30, 2025. Results: A total of 46 pts were enrolled across 7 medical centers in Taiwan. Among them, the majority of pts exhibited favorable clinical characteristics, including stage III disease (63.0%), primary debulking surgery (78.3%) and CR (56.5%) to 1LCT. 84.8% of pts were BRCA wild-type, 21.7% were categorized as HRD-negative, while HRD status remained unknown in 45.7% of pts. For the PFS analysis of clinical effectiveness, we further excluded 2 pts who received niraparib for less than 30 days and 3 pts who had no tumor assessment recorded either before or after the start of 1LMT. After a median follow-up of 14.9 months, the median PFS (mPFS) was not reached (NR), and the 12-month PFS rate was 75.6% in the overall population. In subgroup analyses, the mPFS for BRCA wild-type/HRD-positive and HRD-negative pts was NR and 20.8 months, respectively, with corresponding 12-month PFS rates of 81.8% and 74.1%. Conclusions: These interim effectiveness results support niraparib as an effective 1LMT for newly diagnosed advanced OC pts in the Taiwanese population, demonstrating consistent benefit across all genetic subgroups. Ongoing long-term follow-up will further substantiate the durability of niraparib’s benefit in a real-world setting. Summary of mPFS by genetic subgroup. Pt Number, N mPFS, month 12-month PFS rate, % All Pts 41 NR 75.6 BRCA status BRCA m 4 NR 100.0 BRCA wt 35 NR 75.3 BRCA unknown 2 NR 100.0 HRD status HRD+ 14 NR 85.1 BRCA wt/HRD+ 11 NR 81.8 HRD- 9 20.8 74.1 HRD unknown 18 NR 75.2

Clinical and translational study of p38 inhibitor pexmetinib plus nivolumab following anti–PD-1/L1 failure in advanced solid tumors.

2515 Background: Cancers resistant to immune checkpoint blockade typically harbor a non-T cell-inflamed phenotype, characterized by low type I/II interferon activity and limited CD8⁺ T-cell infiltration within the tumor microenvironment. We previously identified p38 MAPK activation as a tumor-intrinsic immune exclusion mechanism associated with resistance to immunotherapy across solid tumors. Based on these preclinical observations, we conducted a Phase II clinical trial (NCT04074967) combining pexmetinib, a p38 inhibitor, with nivolumab in advanced solid tumors. Here, we report safety, clinical activity, and translational results in patients with PD-1 refractory head and neck (HN) cancer and lung cancers. Methods: Patients received pexmetinib 200 mg orally once daily plus nivolumab 480 mg intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) assessed by RECIST v1.1. Translational analyses included pharmacodynamic assessment, plasma proteomics, single-cell RNA sequencing (scRNAseq), and computed tomography-based radiomic analyses. Results: Thirty-five patients were enrolled (HN cohort = 11 [31%; 100% squamous cell carcinoma]), lung cohort = 24 [69%; 63% adenocarcinoma]). Median age was 62 years; 60% were male and 89% had ECOG performance status 1. Twenty-nine patients were radiographically evaluable. Partial responses were observed in four patients (ORR 14%), and 13 patients (45%) experienced stable disease. Median duration of response was 11.1 months. Median progression-free survival (PFS) was 7.2 months and overall survival (OS) was 9.3 months. Treatment-related adverse events (TRAEs) of any grade occurred in 89% of patients; 47% experienced grade ≥3 TRAEs. No fatal TRAEs were reported. Plasma proteomic profiling identified on-treatment immune modulation relative to baseline, with increased T cell-associated cytokines/chemokines in patients with durable clinical benefit (PFS > 6 months). Among three patients with paired pre- and on-treatment tumor scRNAseq, an increase in intratumoral T-cell abundance was observed in one patient with tumor shrinkage but not in two patients with progressive disease. On-treatment increases in T-cell radiomic score relative to baseline were significantly greater in responders vs. non-responders, and were associated with improved PFS and OS ( P < 0.05). Conclusions: In patients with PD1-refractory HN cancer and lung cancers, pexmetinib plus nivolumab demonstrated an acceptable safety profile and durable clinical benefit. Multimodal translational profiling revealed increased inflammatory cytokine signaling and radiomic and molecular features consistent with enhanced CD8⁺ T-cell engagement in responders. These findings suggest that targeting tumor-intrinsic p38 MAPK may represent a mechanistically informed strategy to overcome immunotherapy resistance. Clinical trial information: NCT04074967 .

Safety and efficacy of immunotherapy rechallenge in solid tumors after discontinuation of immune checkpoint inhibitors for immune-related adverse events: A systematic review and meta-analysis.

11127 Background: Immune-related adverse events (irAEs) often require treatment discontinuation in patients with cancer receiving immune checkpoint inhibitors (ICIs). Given limited subsequent treatment options, ICI rechallenge is frequently considered. We aimed to estimate the incidence of recurrent irAEs and objective response rates (ORR) in patients receiving ICI rechallenge following prior irAEs. Methods: PubMed, Web of Science, and Embase were searched for studies evaluating ICI rechallenge in patients with advanced solid tumors who previously suspended treatment due to irAEs. Outcomes included the incidence of grade 1-5 (Gr1-5), Gr1-2, and Gr3-5 irAEs, recurrent irAEs, new irAEs, ORR, and disease control rate (DCR). Random-effects meta-analyses and subgroup analyses by cancer type were performed. Meta-regression analysis was conducted to evaluate the impact of the grade and type of initial irAEs on response outcomes. Heterogeneity was assessed using I 2 statistics (≥50% considered high). Results: Thirty-seven studies comprising 1,126 patients with initial irAEs (Gr1-2: 62.8%, Gr3-4: 37.2%) leading to suspension of ICIs were included. The most common initial irAEs in the pooled cohort were hepatitis/liver enzyme elevations (20.5%), pneumonitis (16.1%), and nephritis/acute kidney injury (14.8%). Pooled incidences of Gr1-5, Gr1-2, and Gr3-5 irAEs after ICI rechallenge were 42.2% (95% confidence interval [CI]: 35.3-49.3), 27.1% (95% CI: 22.9-31.7), and 18.8% (95% CI: 14.7-23.8), respectively. Subgroup analysis showed overall higher incidences of irAEs in melanoma (Gr1-5: 54.6%, Gr1-2: 23.2%, Gr3-5: 26.4%) than those in lung cancer (Gr1-5: 39.7%, Gr1-2: 27.4%, Gr3-5: 14.0%) and solid tumors (Gr1-5: 36.7%, Gr1-2: 22.8%, Gr3-5: 20.1%). The same type of irAEs recurred in 23.8% (95% CI: 20.1-28.0) of patients, while new types of irAEs developed in 29.3% (95% CI: 25.2-33.7) of patients undergoing ICI rechallenge. The overall ORR was 45.2% (95% CI: 34.5-56.4), with cancer type-specific ORRs of 60.5% (95% CI: 47.9-71.9) in melanoma, 39.1% (95% CI: 17.4-66.2) in lung cancer, and 39.5% (95% CI: 27.7-52.6) from studies investigating solid tumors. DCR was high across cancer types: 77.3% (95% CI: 67.7-84.7) overall, 68.2% (95% CI: 41.3-86.8) in melanoma, 91.2% (95% CI: 67.7-98.1) in lung cancer, and 72.5% (95% CI: 63.3-80.1) in solid tumors. Meta-regression analysis showed that commonly observed initial irAE types or grades of initial irAEs (Gr1-2 vs. Gr3-4) did not significantly impact ORR or DCR. Conclusions: ICI rechallenge after discontinuation due to irAEs demonstrates clinical activity but carries a substantial risk of both recurrent and new irAEs. These findings highlight the need for predictive biomarkers to optimize patient selection and maximize survival without compromising safety.

Consideration of adjusted ideal body weight dosing in BG-C9074 (B7-H4–targeting ADC) from pharmacokinetics, efficacy, and safety perspectives.

3029 Background: B7-H4 is a transmembrane glycoprotein that is upregulated in a variety of solid tumors. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4. We present results of the pharmacokinetic (PK) and exposure-response (ER) analyses supporting the implementation of adjusted ideal body weight (AiBW)-based dosing in the ongoing phase 1 study. Methods: BG-C9074-101 (NCT06233942) is a first-in-human, multicenter study designed to assess BG-C9074 as monotherapy and in combination with other anticancer therapies in patients (pts) with advanced solid tumors. Total body weight (TBW) and AiBW-based dosing were evaluated at 1-7 mg/kg and 6.5-9 mg/kg, respectively, administered intravenously every 3 weeks. PK samples were collected to measure serum ADC and plasma free P1021 payload analytes at Cycle 1 and steady state (Cycle 5). A population PK model, incorporating both ADC and payload, was developed and used to evaluate safety and efficacy ER relationships. Results: As of October 30, 2025, PK, safety, and efficacy data were available for 107 pts with advanced solid tumors. TBW dosing of BG-C9074 led to a maximum tolerated dose < 7 mg/kg. The ADC and free payload exposures increased with BW for TBW dosing, while ADC clearance moderately increased with BW leading to higher exposure in high BW patients (Table 1). Higher ADC exposure was associated with an increased incidence of Grade ≥3 treatment-related adverse events (TRAEs), predominantly neutropenia. Early dose modifications and use of granulocyte colony-stimulating factor were more frequent at higher doses and exposures. Increased and sustained tumor shrinkage observed in pts with ovarian cancer (OC) with higher ADC exposure. AiBW enabled a higher tolerable dose at 8 mg/kg, by normalizing ADC and payload exposure across all bodyweight ranges. Conclusions: AiBW dosing effectively reduced PK variability compared with TBW dosing, providing more consistent exposure across BW. Higher ADC exposure was associated with increased efficacy, but also with a higher incidence of manageable TRAEs. AiBW optimizes the risk-benefit profiles across BW. Clinical trial information: NCT06233942 . Underweight(<18.5 kg/m 2 ) Normal(18.5-24.9 kg/m 2 ) Overweight(25-29.9 kg/m 2 ) Obese(≥30 kg/m 2 ) Simulated Cycle 1Median ADC exposure at 7 mg/kg TBW (ng/mL) 352 464 533 626 Simulated Cycle 1 Median ADC exposure at 7 mg/kg AiBW (ng/mL) 411 448 464 481 ADC Exposure Tertile 1 2 3 Grade ≥3 TRAE 16.2% (6/37) 27.8% (10/36) 37.8% (14/37) Grade ≥3 Neutropenia 10.8% (4/37) 19.4% (7/36) 27% (10/37) Dose modifications 16.2% (6/37) 19.4% (7/36) 27% (10/37) Median tumor shrinkage in OC at Week 24 Tumor Assessment (N=25) −28.9% −33.3% −48%

Molecular characteristics of therapy-related myeloid neoplasms in PARP inhibitor–treated patients.

6597 Background: Poly ADP-ribose polymerase inhibitors (PARPi) are part of standard therapy in solid tumors, and is associated with development of therapy-related myeloid neoplasm (t-MN), including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The contribution of pre-existing clonal hematopoiesis (CH) in t-MN with PARPi exposure is unknown. We report outcomes of a real-world cohort of t-MN patients following PARPi therapy. Methods: We performed a retrospective single-center analysis of 23 patients with solid tumors treated with PARPi (olaparib, rucaparib, niraparib, talazoparib) who subsequently developed t-MN. Chart review was performed to collect clinical data. Blood samples collected as a somatic control prior to the first chemotherapy or radiation for targeted next-generation sequencing (NGS) using the MSK-IMPACT platform were analyzed for pre-existing CH in a subset of evaluable patients (n=17). CH was defined as a somatic mutation with variant allelic frequency of 2% or more in peripheral blood. Results: Median age was 63 years at initial solid tumor diagnosis and 68 years at t-MN diagnosis. Primary malignancies included Ovarian/Fallopian Tube (83%, n=19), Breast (17%, n=4), Prostate (9%, n=2), and Esophageal (n=1) cancer. 3 patients had a history of both Breast and Ovarian cancer. Germline BRCA1/2 mutations were present in 48% (n=11) and 1 patient had Li-Fraumeni. Median time from PARPi initiation to t-MN diagnosis was 23.7 months (range: 1.6–45.3 months). At t-MN diagnosis, 52% (12/23) presented with MDS (including one case of clonal cytopenias of undetermined significance) and 48% (11/23) with AML. Genomic profiling of t-MN showed 78% (18/23) of patients had TP53 mutations, and 65% (15/23) had complex karyotype. 90% of evaluable AML cases were classified as adverse risk by ELN 2022 and most MDS cases (9/11) had High/Very High risk by IPSS-R. Median overall survival in this cohort was 6 months from t-MN diagnosis. Among 17 patients with evaluable baseline blood samples, 41% (7/17) had detectable CH prior to t-MN, while 59% (10/17) did not. Of those with pre-existing CH, 57% (4/7) harbored mutations in DNA damage response genes (2 with TP53 , 2 with PPM1D ). Other mutations included DNMT3A (N=2), ASXL1 (N=1), SRSF2 (N=1), and JAK2 (N=1). 43% (3/7) had a single CH mutation, while 57% (4/7) had 2 or more CH mutations. 6/7 of those with pre-existing CH had molecular testing at t-MN diagnosis, all of which (6/6) had a detectable TP53 mutation at t-MN diagnosis, even when not previously detected. Cytogenetic features of t-MN for those with and without pre-existing detectable CH were similar. Conclusions: This is the largest single center cohort of post-PARPi t-MN with molecular characteristics described to date. Further study on the effect of PARPi therapy in the pathogenesis of t-MN is needed.

Expression of Concern: Identification of stable heat tolerance QTLs using inter-specific recombinant inbred line population derived from GPF 2 and ILWC 292

Nanomedicine approaches for Alzheimer’s disease: Advances in drug delivery and theranostic applications

Freeform Manufacturing of Plant‐Based Structural Colors for Scalable Photonic and Mechanochromic Devices (Adv. Mater. 35/2026)

Recent Advances in Electrospun Nanofibers for Triboelectric Nanogenerators: Performance Enhancement Strategies and Emerging Applications

ABSTRACT In the quest for next‐generation sustainable energy systems, triboelectric nanogenerators (TENGs) have emerged as a pivotal technology for converting mechanical energy into electrical power, especially at the micro and nanoscale. Among various structural platforms, fibrous materials, particularly those produced via electrospinning, have demonstrated exceptional potential for TENG development due to their tunable morphology, lightweight nature, mechanical flexibility, and large surface‐to‐volume ratio. These characteristics are critical for enhancing the interfacial charge generation and transfer that underpin triboelectric performance. This review offers a comprehensive examination of the latest advances in fibrous materials for TENGs, with a particular focus on material innovations, structural design strategies, and performance optimization techniques. Emphasis is placed on the role of hybrid nanocomposites, core–shell configurations, surface functionalization, and alignment control in maximizing electrical output and operational durability. Additionally, the paper surveys emerging application areas such as wearable electronics, self‐powered sensors, smart textiles, biomedical monitoring, and human‐machine interaction systems. By bridging fundamental material science with practical design paradigms, this review identifies critical bottlenecks and lays out future research directions toward scalable, efficient, and environmentally friendly fibrous TENG technologies.

Seal and fish oils partially counteract inflammation and modulate endocannabinoidome lipid and oxylipin alterations in DSS-induced colitis

Molecular analysis of a new patient COX15 mutation provides insight into the etiology of fatal infantile cardioencephalopathy

Molecular profiling of male breast cancer in Brazil: Comprehensive genomic characterization of a Latin American cohort.

571 Background: Male breast cancer (MBC) is a rare disease, accounting for < 1% of all breast cancers. Current treatment recommendations are largely extrapolated from female breast cancer data, which may not reflect the distinct biological features of MBC. Notably, MBC is associated with higher mortality rates than female breast cancer. Molecular data from Latin America are scarce. This study aimed to characterize the clinicopathological and molecular features of MBC in a Brazilian cohort, addressing an important knowledge gap in an underrepresented population. Methods: Medical records of 106 men diagnosed with breast cancer at three Brazilian cancer centers between 2000 and 2022 were reviewed. Tumor samples from 48 patients were available for molecular analysis after centralized histopathological review. FFPE samples with ≥10% tumor cellularity were included. DNA and RNA were extracted using the AllPrep kit (Qiagen). Libraries were prepared using the Oncomine Focus Assay (Thermo Fisher Scientific) and sequenced on the Ion S5 platform. Bioinformatic analysis for single nucleotide variants (SNVs), insertions/deletions, copy number variations (CNVs), and gene fusions was performed using Ion Reporter software. Results: The median age at diagnosis was 58.5 years (range: 33–84). A family history of cancer was reported in 64% of patients, including female breast cancer in 32%. Most tumors were invasive ductal carcinomas (87.7%), high grade (grades 2–3; 90%), and hormone receptor–positive (93%). HER2+/HR– and triple-negative subtypes accounted for 0.9% and 3.9%, respectively. Most patients (88.5%) presented with localized or locally advanced disease. The most frequent pathogenic variants were PIK3CA (28%), followed by MAP2K1, BRAF, and AKT1 (6% each), and EGFR, JAK3, and MTOR (3% each). The most common CNV amplifications involved MYC (24%), FGFR1 (20%), CCND1 (16%), and ERBB2 (4%). No gene fusions were identified. Pathway analysis revealed alterations in PI3K/AKT/mTOR (37%), Cell Cycle (40%), FGF signaling (20%), and MAPK (12%) pathways. Overall, 46% of patients harbored potentially actionable SNVs, and 24% harbored potentially actionable CNVs. Conclusions: This is the first comprehensive molecular characterization of MBC in Brazil. Our findings confirm PIK3CA as the most frequent alteration, consistent with international cohorts, supporting the central role of the PI3K/AKT/mTOR pathway in MBC. Additional alterations in Cell Cycle and FGF signaling pathways highlight distinct oncogenic drivers. The high prevalence of potentially actionable genomic alterations suggests that molecular profiling may inform treatment selection for a substantial proportion of patients. These findings underscore the limitations of extrapolating treatment guidelines from female breast cancer and support biomarker-driven clinical trials for men with breast cancer in Latin America.

A phase II evaluation of sacituzumab govitecan in platinum-resistant ovarian cancer (NCT06028932).

5575 Background: Patients with platinum-resistant ovarian cancer (PROC) have few therapeutic options. More than 60% of high-grade serous ovarian cancers overexpress (≥ 2+ by immunohistochemistry) Trop2, a key regulator of growth pathways and marker of aggressive disease. Sacituzumab govitecan (SG) is an antibody-drug conjugate consisting of a Trop-2–specific antibody conjugated with SN-38, an active metabolite of irinotecan. Methods: NCT06028932 is a single-institution open-label phase II study. Patients received SG at 10 mg/kg intravenously days 1 and 8 of a 21-day cycle until prohibitive toxicity or progression. The primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints included progression-free (PFS) and overall (OS) survival, as well as safety. Results: Twenty patients were enrolled. Median age was 67 years (range: 45-84). Most participants (85%, n=17) were White. The median number of prior lines prior to enrollment was 3 (range: 1-8). ECOG performance status was 0 (n=16) or 1 (n=4). Most patients had a poorly differentiated tumor (90%, n=18) with advanced disease (stage III/IV) at initial diagnosis (85%, n=17). Serous histology predominated (75%, n=15), followed by clear cell (15%, n=3), endometrioid (5%, n=1), and carcinosarcoma (5%, n=1). Across a median follow-up of 9.9 months, there were 15 progressions and 4 deaths. ORR was 35% (7/20); there were no complete responses, and stable disease was achieved in 40% (8/20). Median PFS was 8.0 months (95% CI: 3.8-14.8); median OS was not yet reached. No new safety signals were observed. The most common grade 3-4 treatment-emergent adverse events were neutropenia (n=15), hypokalemia (n=3), and anemia (n=2). The most frequent grade 1-2 events included diarrhea (n=59), fatigue (n=27), abdominal pain (n=20), nausea (n=20), alopecia (n=16), anorexia (n=14), and vomiting (n=13). Conclusions: SG exhibits encouraging efficacy for PROC with manageable toxicities. Future studies are warranted. Clinical trial information: NCT06028932 .

The obesity paradox in colon cancer hospitalizations: Mortality and cardiovascular risk.

e15716 Background: Obesity is a well-established risk factor for colorectal cancer (CRC) and is associated with adverse oncologic outcomes, including increased postoperative morbidity. Proposed mechanisms include adipose tissue–mediated chronic inflammation, insulin resistance, altered adipokine signaling, and gut microbiome dysregulation, all of which may influence tumor biology and clinical outcomes. Despite these associations, an “obesity paradox,” characterized by lower short-term mortality among patients with obesity, has been reported in several oncologic populations. However, data evaluating this phenomenon in hospitalized patients with colon cancer remain limited, particularly with respect to cardiovascular complications and healthcare utilization. This study aimed to evaluate the association between obesity and in-hospital outcomes among patients hospitalized with colon cancer. Methods: A retrospective cohort study was conducted using the 2019–2022 National Inpatient Sample (NIS) database. Adult patients (≥18 years) hospitalized with colon cancer were identified using ICD-10 codes and stratified by the presence of obesity. The primary outcome was in-hospital mortality. Secondary outcomes included race, length of stay (LOS), hospital charges, cardiovascular diseases, and other clinical outcomes. Results: A total of 1,026,965 hospitalizations for colon cancer were identified, of which 143,255 (13%) involved patients with obesity. In-hospital mortality among obese patients was 3,850 (2.7%). Obese patients were more commonly White (72%), had a mean age of 66 years, and demonstrated significantly lower in-hospital mortality compared with non-obese patients (2.7% vs 4.8%; OR 0.55; P < 0.001). Obesity was associated with longer length of stay (coefficient 0.17; P < 0.001), higher hospital charges (coefficient $12,107; P < 0.001), a higher risk of diverticulitis (1.8% vs 1.4%; OR 1.28; P < 0.001), and increased cardiovascular complications, including arrhythmias (19% vs 16%; OR 1.20; P < 0.001) and acute heart failure (5% vs 3%; OR 1.50; P < 0.001), compared with non-obese patients. Conclusions: Among patients hospitalized with colon cancer, obesity was associated with lower in-hospital mortality, supporting the presence of an obesity paradox in the inpatient setting. However, obesity was also associated with increased healthcare utilization and a higher burden of cardiovascular complications. These findings highlight the complex impact of obesity on inpatient outcomes in colon cancer and underscore the importance of risk-stratification strategies that integrate oncologic, metabolic, and cardiovascular factors.

Time-resolved cardiovascular risk after immune checkpoint inhibitors: A large real-world cancer cohort study.

12023 Background: With expanding use of immune checkpoint inhibitors (ICIs), immune-related toxicities increasingly influence outcomes beyond tumor control. Cardiovascular events are among the most consequential yet potentially preventable complications. Given the low incidence of major adverse cardiovascular events (MACE) and their relatively narrow post-initiation window, reliable time-resolved risk estimation requires very large cohorts, which remain scarce, limiting evidence to guide surveillance and prevention. Methods: We conducted a pan-cancer retrospective cohort study (N = 269,257; mean follow-up 4.5 years) using a large real-world cancer registry from Shandong Provincial Center for Disease Control and Prevention. Patients receiving ICIs after their broad clinical implementation were compared with patients treated in the pre-ICI era without immunotherapy, a design chosen to mitigate indication-related differences observed in the contemporary setting. Propensity scores derived from elastic net regularization were used to construct overlap weights for balancing covariates across cohorts. We evaluated MACE, AMI (acute myocardial infarction), and stroke across four prespecified intervals (0–90, 91–180, 181–270, and 271–365 days) using interval-stratified weighted Cox models. Absolute risk differences were further characterized using weighted incidence density differences and restricted mean survival time. Results: All covariates achieved excellent balance (maximum |SMD| = 0.004) after weighting. ICI exposure was associated with higher 1-year MACE risk (HR, 1.17; 95% CI, 1.12–1.23; P < 0.001), corresponding to a weighted incidence density difference of 10.90 per 1,000 person-years (95% CI 8.73–13.06). The largest absolute risk increase was observed during 0–90 days after ICI initiation(weighted incidence density difference, 17.83 per 1000 person-years; 95% CI, 12.43 to 23.24).The risk of AMI peaked early, with a statistically significant association observed only during 0–90 days (HR, 1.86; 95% CI, 1.54–2.24; P < 0.001). In contrast, stroke risk peaked during days 91–180 (HR, 1.27; 95% CI, 1.11–1.44; P < 0.001) and remained significantly elevated through 181–270 days (HR, 1.25; 95% CI, 1.08–1.44; P = 0.003). Stroke accounted for 51% (95% CI: 19% to 83%), 63% (95% CI: 37% to 89%), 66% (95% CI: 43% to 90%), and 67% (95% CI: 45% to 88%) of the total weighted incidence density difference for MACE during days 0–90, 0–180, 0–270, and 0–365, respectively. Conclusions: ICI exposure was associated with temporally heterogeneous cardiovascular risk, with AMI concentrated in the first 90 days and stroke risk remaining elevated thereafter. These results suggest a time-tailored approach to cardio-oncology care, characterized by intensified early monitoring for AMI and sustained attention to stroke prevention in subsequent months.