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Racial and ethnic disparities in survival among patients with early-onset primary liver cancer: A 15-year SEER analysis.

e13749 Background: Early-onset liver cancer is increasingly recognized as a distinct clinical entity, yet population-level outcomes across racial and ethnic groups remain poorly defined. We examined disparities in stage at diagnosis and survival among patients diagnosed with primary liver cancer before age 50. Methods: Patients aged < 50 years with primary liver cancer diagnosed between 2006 and 2021 were identified from the Surveillance, Epidemiology, and End Results Program (SEER) database. Stage at diagnosis was compared by race/ethnicity using chi-square testing. Overall survival (OS) and cancer-specific survival (CSS; liver cancer death) were estimated using Kaplan–Meier methods. Multivariable Cox proportional hazards models evaluated associations between race/ethnicity and survival, adjusting for age, sex, year of diagnosis, and stage. Results: A total of 3,661 patients were included: Non-Hispanic White (35.9%), Non-Hispanic Asian or Pacific Islander (24.8%), Hispanic (24.3%), Non-Hispanic Black (13.5%), and Non-Hispanic American Indian/Alaska Native (1.2%). Overall stage distribution was localized 42.1% (n = 1,541), regional 30.0% (n = 1,097), and distant 27.9% (n = 1,023), with modest variation by race/ethnicity (p = 0.058). Median OS ranged from 9 months in Non-Hispanic Black patients to 22 months in Non-Hispanic White patients. Twelve-month OS was 43.7% in Non-Hispanic Black patients versus 63.2% in Non-Hispanic White patients; 60-month OS was 21.0% versus 34.3%, respectively. On adjusted analysis (reference: Non-Hispanic White), worse OS was observed among Non-Hispanic Black (HR 1.60, 95% CI 1.41–1.81; p < 0.001), Non-Hispanic Asian or Pacific Islander (HR 1.23, 95% CI 1.11–1.37; p < 0.001), and Hispanic patients (HR 1.23, 95% CI 1.11–1.37; p < 0.001). Similar disparities were seen for CSS, with the highest risk among Non-Hispanic Black patients (HR 2.19, 95% CI 1.84–2.60; p < 0.001). Table 1 below shows survival estimates. Conclusions: Significant racial and ethnic disparities in OS and CSS persist among patients with early-onset primary liver cancer, independent of stage at diagnosis. Kaplan–Meier survival estimates by race/ethnicity. Race/Ethnicity Median OS (mo) OS 12 mo OS 60 mo Liver Cancer Death (%) Non-Hispanic White 22 63.2% 34.3% 26.3 Non-Hispanic White 9 43.7% 21.0% 43.6 Non-Hispanic Asian/PI 12 49.5% 28.7% 46.0 Hispanic (All Races) 15 54.2% 26.5% 30.3 AI/AN 27 70.2% 29.4% 29.5

Performance status and tarlatamab outcomes in a large, multi-institution real-world database of 2L+ ES-SCLC.

e20120 Background: Tarlatamab is a novel bispecific T-cell engager approved for 2L+ extensive stage small cell lung cancer (ES-SCLC). Previously published real-world single-institution studies have been small (n=22) and (n=39); in both, tarlatamab resulted in inferior survival with higher rates of CRS and ICANS than observed in the DeLLphi-304 trial. To better understand real world outcomes with tarlatamab, we examined a much larger, multi-institutional dataset. Methods: Utilizing the US-based, electronic health record-derived, deidentified Flatiron Health Research Database, patients with ES-SCLC treated with tarlatamab between 3/2024 and 09/2025 were selected. Baseline characteristics, treatment history, and clinical outcomes were abstracted. Chi-square and t-tests were used for used for univariate analysis. Median time to treatment discontinuation (mTTD), real-world progression-free survival (mPFS) and overall survival (mOS) from start of tarlatamab were estimated via Kaplan Meier curves. Effects of patient baseline characteristics were estimated via log-rank analysis and Cox regression. Results: Of 204 patients included, 90 (44%) were female. Median age at start of therapy was 66.4 years. 158 (77%) were white, 24 (12%) Black. At initiation of tarlatamab, 62 (30%) patients were ECOG PS 0, 86 (42%) were 1, 48 (24%) were 2+. 75 (37%) received tarlatamab in 2L, 64 (32%) in 3L, and 65 (31%) in 4L+. 109 (53%) patients previously received lurbinectedin; only 15 (7%) received subsequent therapy. mPFS from start of tarlatamab was 3.8 months(m), mTTD was 2.3m, and mOS was 11.2m. Patients treated in 2L had mPFS of 5.3m and mOS of 12.2m, compared to 3.4m (p=0.36) and 8.1m (p=0.81) in 3L+. Patient sex, race (Black vs White) and age (<65 vs ≥65yo) were not associated with TTD, PFS, or OS (Table 1). ECOG ≥2 PS was associated with shorter mPFS vs ECOG 0-1 (2.1 vs 4.5; p=0.004), mTTD (1.6 vs 2.8; p=0.001) and mOS (3.2 vs 13.4; p<0.001) vs ECOG 0-1. Conclusions: In the largest retrospective analysis to date, mTTD, mPFS, and mOS with tarlatamab in pts with intact PS (0-1) appear similar to outcomes reported in DeLLphi-304. However, ECOG PS ≥2 was associated with significantly shorter TTD, PFS, and OS, which may account for inferior real-world outcomes compared to the trial. Line of therapy in our cohort was not associated with outcomes, nor was race, sex or age. Baseline characteristics and survival. Table 1 mPFS p-value mTTD p-value mOS p-value All 3.8 2.3 11.2 2L 5.3 P=0.44 2.8 P=0.33 12.2 P=0.92 3L+ 3.4 2.0 8.1 Female 3.8 P=0.96 2.4 P=0.61 13.4 P=0.88 Male 3.9 2.3 11.2 Black 3.5 P=0.66 2.4 P=0.45 11.2 P=0.75 White 4.7 2.2 13.8 Age <65 3.9 P=0.74 2.7 P=0.90 12.8 P=0.66 Age≥65 3.6 2.2 11.0 ECOG 0-1 4.5 P=0.004 2.8 P=0.001 13.4 P=0.002 ECOG 2+ 2.1 1.6 3.2 Values in months. Sig p-value (<0.05) in bold.

RegeNovar: A phase I/II study of ubamatamab plus carboplatin, paclitaxel, and bevacizumab as salvage therapy in ovarian cancer with poor response to first-line chemotherapy.

TPS5640 Background: Patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant platinum-based chemotherapy who are not amenable to complete interval cytoreductive surgery (ICS) due to poor chemosensitivity—defined by a CA-125 KELIM score <1.0—have a particularly poor prognosis, with approximately 20% 5-year overall survival. Ubamatamab is a human IgG4-based bispecific antibody targeting MUC16 (CA-125–expressing ovarian cancer cells) and CD3+ T cells and has demonstrated clinical activity in platinum-resistant recurrent ovarian cancer (Lee et al, Proc ESMO 2025). We hypothesize that adding ubamatamab to standard carboplatin–paclitaxel–bevacizumab may enhance tumor response and improve surgical resectability in patients with advanced high-grade EOC with poor chemosensitivity and disease not amenable to complete ICS after initial neoadjuvant chemotherapy. Methods: RegeNovar (EuCT 2025-524232-20-00) is an academic, multicenter phase I–II trial enrolling patients with stage III–IV high-grade EOC who, after 3–4 cycles of standard neoadjuvant carboplatin–paclitaxel administered every 3 weeks, present two poor prognostic features: (1) unfavorable standardized KELIM score <1.0, and (2) disease considered not amenable to complete ICS. The trial includes two sequential parts: (i) a phase I safety run-in to evaluate the safety of ubamatamab in combination with carboplatin–paclitaxel–bevacizumab and confirm the recommended phase II dose (RP2D); and (ii) a phase II efficacy part assessing the antitumor activity of this combination. Patients receive carboplatin AUC5 ; paclitaxel 175 mg/m²; and bevacizumab 15 mg/kg Q3 weeks for three cycles. Ubamatamab is administered with weekly step-up dosing during cycle 1, followed by a fixed dose of 800 mg Q3 weeks during cycles 2 and 3. Feasibility of complete late cytoreductive surgery is evaluated after three cycles of the study regimen. Subsequent maintenance treatment consists of olaparib plus bevacizumab for patients with BRCA-mutated or HRD-positive tumors, or ubamatamab plus bevacizumab for up to 15 months in patients with HRD-negative tumors. The primary endpoint of phase I is safety, including treatment-related adverse events (NCI CTCAE v6.0), DLT within the first 4 weeks, and RP2D determination using a BOIN design targeting a DLT probability ≤28%. The primary endpoint of phase II is the objective response rate (ORR) after three cycles per RECIST 1.1 (H0 5%, H1 30%, one-sided α=5%, power=80%). Total 31 to 43 patients are required, depending on potential need for dose de-escalation. Secondary endpoints include ORR, duration of response, disease control rate, rate of late cytoreductive surgery, PFS, OS, and progression-free survival during subsequent therapy. The trial is sponsored by ARCAGY-GINECO, conducted in 12 French centers, and funded by Regeneron. Clinical trial information: EuCT 2025-524232-20-00.

Tissue-free minimal residual disease evaluation and clinical utility in early breast cancer: A real-world study.

3052 Background: Minimal residual disease (MRD) detected using circulating tumor DNA (ctDNA) is associated with increased breast cancer (BC) relapse risk in patients (pts) with early BC after curative-intent surgery. However, the clinical utility of ctDNA-based MRD testing for post-surgical surveillance and risk stratification remains incompletely defined. We used real-world data to evaluate the performance of Guardant Reveal, a tissue-free epigenomic assay for MRD detection, and the clinical significance of a positive MRD test (+MRD) in pts with resected early BC. Methods: Data of pts with resected stage I-IIIA BC in the Guardant InfinityAI Data Library who underwent Guardant Reveal testing between February 2023 and September 2025 was analyzed. Pts with ≥1 post-surgical MRD were included if they had either no distant metastatic BC recurrence with ≥1 year of follow up after the last MRD test or a documented distant metastatic BC postoperatively; pts with a new non-breast primary malignancy were excluded. Sensitivity was assessed by site of distant metastasis and interval from MRD test to recurrence; nodal recurrences were excluded due to claims data limitations. Specificity was assessed using all tests from pts without recurrence and ≥1 year of follow up after the last post-treatment MRD test. Claims data were used to infer treatment changes following +MRD. Results: A total of 822 pts was analyzed. 114 pts with real-world clinico-genomics data were evaluable for sensitivity and 708 for specificity. One-year sensitivity for distant metastatic recurrence was 71%, and was highest for bone-only (97%, 35/36 cases) or lung (89%, 8/9 cases) recurrences and lowest for brain-only recurrences (33%, 1/4 cases). Sensitivity within 12 months of recurrence was higher in hormone receptor-positive (HR+)/HER2-negative BC (79%) and stage IIIA BC (81%) and for multiple-organ versus single-organ metastasis (83% versus 69%). Sample-level specificity was 94%. Following +MRD, 41 pts did not initiate or switch systemic therapy; 29 had distant BC recurrence, including 24 within 90 days after +MRD. Twenty pts switched therapy within 90 days of +MRD; 19 recurred, including 17 within 90 days after +MRD. Among 10 pts with post-recurrence MRD testing, only 3 had +MRD. Conclusions: In a real-world cohort of pts with resected early-stage BC, a tissue-free epigenomic ctDNA MRD assay demonstrated high specificity and clinically meaningful sensitivity for distant metastatic recurrence, particularly for bone-only and lung metastases and in pts with HR+ BC. These findings support ctDNA-based MRD testing as a noninvasive tool for postsurgical surveillance and risk stratification in early BC.

Prognostic significance of teratoma components in germ cell tumor patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

5028 Background: The prognostic significance of a teratoma component in relapsed or refractory germ cell tumors (GCT) treated with high-dose chemotherapy followed by autologous stem cell transplantation (HDCT-ASCT) remains unclear. While teratoma has been extensively studied in earlier treatment lines, data specifically addressing its impact in the transplant setting are limited. Identification of factors influencing outcomes after HDCT is critical for patient selection and treatment optimization. Methods: This single-center retrospective study included 132 GCT patients who underwent autologous stem cell–supported HDCT. Primary tumor specimens were re-evaluated by an experienced pathologist for the presence of a teratoma component. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared between teratoma-positive and teratoma-negative groups. Univariate Cox regression and predefined subgroup analyses were performed to identify factors associated with survival outcomes. Results: Baseline pathological data were available for 132 patients; 59 (44.7%) had a teratoma component and 73 (55.3%) did not. Baseline clinicopathological characteristics, including age, primary tumor site, stage, IGCCCG risk group, metastatic pattern, biomarker status, and response to first-line therapy, were comparable between groups. After a median follow-up of 55.6 months, median PFS was 6.8 months (95% CI, 4.1–9.6). Median PFS was significantly shorter in teratoma-positive patients compared with teratoma-negative patients (5.6 vs 10.0 months; log-rank p = 0.011). The 2-year PFS rates were 34% and 50%, respectively. Teratoma presence was associated with inferior PFS in univariate analysis (HR 1.77, 95% CI 1.13–2.77; p = 0.013). Median OS was not reached overall; median OS was 68.9 months in teratoma-positive patients and not reached in teratoma-negative patients, with no significant difference between groups (p = 0.986). The 2-year OS rates were similar (64% vs 67%). Subgroup analyses showed numerically poorer OS with teratoma across most strata, without statistical significance. Conclusions: In relapsed or refractory GCT patients undergoing HDCT, the presence of a teratoma component was associated with inferior disease control but not with a statistically significant OS disadvantage, possibly due to limited follow-up. Teratoma status may help identify patients requiring more intensive transplant strategies and early post-transplant treatment optimization. Prospective studies with longer follow-up are warranted.

Multidisciplinary care in head and neck squamous cell carcinoma: A retrospective analysis at a safety-net hospital.

e18117 Background: Optimal HNSCC management requires coordinated multidisciplinary care including dental evaluation, nutrition support, speech-language pathology (SLP), and audiology. National guidelines recommend early integration of supportive services, but adherence in real-world safety-net settings is variable. We evaluated patterns of multidisciplinary involvement and supportive care utilization. Methods: A retrospective chart review was conducted on 58 patients with HNSCC treated curatively from 2019–2024. Data collected included utilization and timing of dental evaluation, SLP, nutrition, audiology, and percutaneous endoscopic gastrostomy (PEG) tube placement. Weight change from diagnosis through treatment and at 6 months post-treatment was assessed as a marker of nutritional impact. Results: Pre-treatment dental evaluation occurred in 62.5% of evaluable patients. SLP evaluation occurred in 43.9% pre-treatment, with 22.8% receiving ongoing follow-up. Nutrition evaluation occurred in 66.7% pre-treatment, with 43.9% receiving continued follow-up. Audiology evaluation was rare (4.0%). Forty-nine patients were eligible for PEG tube placement; nine deferred or declined. Patients with pre-treatment nutrition evaluation experienced less weight loss during treatment (8.7 kg vs 10.8 kg) and at 6 months post-treatment (11.8 kg vs 14.1 kg). Year-to-year rates of pre-treatment multidisciplinary evaluation varied without consistent improvement. Conclusions: Multidisciplinary supportive care utilization varied among patients with HNSCC in this population. Early nutrition evaluation was associated with less treatment-related weight loss. These findings support efforts to standardize multidisciplinary pathways and optimize supportive care integration during curative-intent treatment.

External validation of new prostate cancer risk groups by PSMA-PET (PPP3).

5112 Background: Previously, we proposed novel risk group definitions for prostate cancer patients based on Prostate-Specific Membrane Antigen (PSMA) targeted positron emission tomography (PET). PSMA-PET pan-stage nomograms (PPP3) were developed using the international, multicentre PROMISE registry (NCT06320223) to prognosticate overall survival (OS). Here, we present an external validation of PPP3. Methods: Eligible patients enrolled into our PROMISE registry database after the PPP3 data cap were included into this external validation study. Included patients had histologically proven prostate cancer and underwent PSMA-PET at hospitals in Turkey, Cyprus, Italy, China, South Africa or Germany between 2015 and 2022. PSMA-PET was standardized by PROMISE version 2 (V2); total lesion count, total tumor volume, PSMA expression score and OS follow-up were obtained as per local site practice. PPP3 nomograms were applied to calculate risk groups and Harrell´s C-indices for the external validation cohort. Calibration curves were measured for 5-year OS. Head-to-head comparison between the visual PPP3 nomogram and the simplified risk stratification table was examined by area under the receiver operating characteristics curve (ROC-AUC). Results: 1855 male patients across all disease stages with 179 (9.6%) reported deaths and median OS follow-up of 4.8 years (IQR 3.7-6.1) were analysed. In the external validation cohort C-indices (95% CI) were 0.71 (0.67-0.76) for the visual nomogram and 0.73 (0.69-0.77) for the quantitative nomogram, respectively. By simplified risk stratification table, 77 of 1855 patients (4.2%) were underestimated and 16 (0.9%) were overestimated, when compared with visual nomograms. Prognostic accuracy was comparable using both methods (AUC Nomogram: 0.64 vs. AUC Table: 0.63, p = 0.02). Conclusions: PPP3 nomograms were validated in an external multi-site patient cohort. Prognostication was accurate (C-indices > 0.70) for both PPP3 nomograms. Clinical trial information: NCT06320223 .

Corrigendum to “Theoretical study in comparison of astatine adsorptions on metal carrier materials for targeted alpha therapy applications” [Next Nanotechnol. 8 (2025) 100231]

Plastic‐Deformation‐Free Fabrication of Freestanding Metal Chalcogenide Ribbons for High‐Performance Flexible Thermoelectric Generators

ABSTRACT Ductile metal chalcogenide semiconductors are intriguing candidates for sustainable, high‐performing flexible thermoelectric generators (f‐TEGs). Processing bulk ductile semiconductors into flexible ribbons relies heavily on plastic deformation; however, such deformation inevitably induces defects that cause detrimental carrier scattering. Furthermore, processing low‐plasticity semiconductors via plastic deformation is particularly challenging, as their inherent brittleness predisposes them to fracture under stress. Herein, we develop a melt spinning strategy that avoids plastic deformation and directly enables the efficient and scalable fabrication of freestanding p‐type CuAg(Te,Se,S) and n‐type Ag 2 (Se,S) flexible ribbons even some of the chalcogenides possess low plasticity. Facilitated by the synergy of thin thickness, tuned compositions and refined microstructures, the ribbons with optimized compositions exhibit excellent flexibility. Moreover, modulating the chalcogen compositions endows the flexible ribbons with superior near‐room‐temperature power factors, peaking at 1618 and 879 µW m −1 K −2 for n‐type Ag 2 Se 0.8 S 0.2 and p‐type CuAgTe 0.9 Se 0.04 S 0.06 , respectively. Notably, the in‐plane f‐TEGs assembled from highly flexible CuAg(Te,Se,S) and Ag 2 (Se,S) ribbons possess impressive normalized power densities that compare favorably to those of f‐TEGs constructed from organic thermoelectrics or inorganic–organic composites. This work provides a useful plastic‐deformation‐free paradigm for fabricating freestanding metal chalcogenide ribbons with high flexibility and thermoelectric properties toward the applications in wearable electronics.

Role of transcript-based HER2 quantification in classification and determining therapeutic eligibility.

e15195 Background: Immunohistochemistry (IHC) is widely used to determine human epidermal growth factor receptor 2 (HER2) expression for tumor classification and treatment eligibility; however, its semi-quantitative and observer-dependent nature may underestimate biologically relevant HER2 activity. The clinical efficacy of trastuzumab deruxtecan (T-DXd, Enhertu) in HER2-low and ultralow tumors has challenged IHC-based stratification, prompting the need for more objective biomarkers such as bulk mRNA sequencing. Methods: We analyzed ERBB2 (HER2) transcript expression in three cancers—breast, colorectal, and osteosarcoma—classified as HER2-low or negative by IHC. Normalized RNA-sequencing data were benchmarked against matched normal tissues from the corresponding organ of origin. In addition, we included a coverage analysis to confirm mature mRNA expression and to reveal transcript variant distribution. In addition, we carried out an independent analysis on the data of The Metastatic Breast Cancer Project dataset to assess the frequency of HER2-low and HER2-negative tumors with aberrant HER2 expression on mRNA level. Results: All tumors demonstrated elevated HER2 transcription, with two exceeding the full expression range of normal tissues and one reaching the 89th percentile. Coverage analysis confirmed the presence of mature, spliced HER2 transcripts, and isoform analysis identified upstream 5′ untranslated-region (UTR) variants as well as the Δ16 splice variant associated with constitutive receptor activation. Independent analysis of the Metastatic Breast Cancer Project dataset similarly revealed that substantial subsets of HER2-low and HER2-negative tumors exceed the 95th and even the 99th percentiles of normal breast expression. Conclusions: These findings demonstrate that transcript-level profiling provides an objective and sensitive measure of clinically meaningful HER2 activity that may be missed by IHC, offering a rational framework for personalized treatment selection and potentially expanding therapeutic options for patients otherwise deemed ineligible for targeted therapy.

Understanding perceptions and barriers to clinical trial participation in multicultural communities.

e13502 Background: Racial, ethnic, and linguistic minorities remain underrepresented in clinical trials. While structural barriers to enrollment are well documented, patient perceptions and cultural factors influencing participation remain understudied. This study aims to assess patient perceptions and barriers to trial participation and identify community engagement opportunities. Methods: A 46-item cross-sectional survey of adult patients and caregivers was verbally administered at Northwell Cancer Institute at Rego Park and assessed demographics, perceptions of clinical trials, motivating and hesitating factors influencing trial participation, and community characteristics. Open-ended responses were thematically analyzed. Likert-scale ratings ranged from 1 (not at all important) to 5 (very important) and were analyzed quantitatively via descriptive statistics. Group comparisons were evaluated using χ² tests. Results: A total of 158 surveys (136 in English) were collected from June to August 2025. Respondent demographics are reported in Table 1. Knowledge of the term “clinical trial” varied, with 22% unable to define the term. Common motivators for trial participation included physician recommendation, quality of life improvement, and immediate health benefits. Frequently cited hesitations included uncertainty about treatment outcomes, side effects, and fear of being treated as a “guinea pig.” Among Likert items, shared language with care team (mean score = 4.5) and doctor’s recommendation (mean score = 4) were the most important drivers to participation. Highest-rated barriers were distance from trial sites (mean score = 3.8) and need for additional support (mean score = 3.8). Perceived importance of patient-physician cultural concordance varied significantly by ethnicity (p = 0.03), income level (p = 0.05), and language (p < 0.001). The perceived importance of requiring additional support in order to participate in trials varied by insurance status (p < 0.05). The perceived importance of shared language did not differ across groups. Conclusions: Our findings in a diverse, urban population revealed drivers and barriers to clinical trial participation with select differences in perceptions observed across demographic groups. Understanding these differences lays the groundwork for our next phase of community engagement. Characteristics N (%) Relationship to Patient Self Caregiver 142 (90)16 (10) Sex Male Female 55 (35)103 (65) Race/Ethnicity NH White NH Black NH Asian Hispanic/Latinx Other/Unknown 42 (27)36 (23)21 (13)44 (28)15 (9) Preferred Language to Speak English Other 105 (66)53 (34) Income <50 K ≥50 K Not Disclosed 48 (30)61 (39)49 (31)

Updated efficacy, safety, and exploratory biomarker analyses of a phase II trial of abemaciclib plus hormonal therapy in recurrent ovarian (OC) and endometrial cancer (EC).

5516 Background: We evaluated abemaciclib with hormonal therapy in patients with estrogen receptor positive (ER+) EC, low-grade serous OC (LGSOC), and selected high-grade serous OC (HGSOC) with CDK4/6 molecular activation features in a single-center, phase II study. Preliminary results demonstrated a 24-week progression-free survival (PFS) rate of 53% in ER+ EC and 60% in LGSOC (2025 SGO Abstract 256). Here, we report the final clinical outcomes and present the first exploratory biomarker analyses from this study. Methods: Abemaciclib was administered at 150mg twice daily in combination with hormonal therapy. The primary endpoint was 24-week PFS; secondary endpoints were median PFS (mPFS), disease control rate (DCR), objective response rate (ORR) and safety. Exploratory analyses evaluated efficacy by TCGA molecular subgroups and tumor next-generation sequencing–defined alterations. PFS was estimated using Kaplan–Meier and compared using log-rank. Results: As of December 2, 2025, 43 patients (21 HR+ EC, 14 LGSOC, 8 HGSOC) were evaluable, with a median follow-up of 29 months (mos). Median age was 64 (range 24-78) and median prior lines of therapy was 3 (range 1-13). Among 21 patients with ER+ EC, the 24-week PFS rate was 56.1% (95% CI 34.5–77.7), mPFS was 9.0 mos (2.4–11.3), DCR was 63%, and ORR was 21%, including one complete response. There were 13 (62%) NSMP, two (10%) MSI-high, two (10%) TP53-abnormal, one (5%) POLE-mutated, and three without molecular data. The NSMP group had 24-week PFS rate and mPFS of 59.8% (32-87.3%) and 10.4 mos (2.4-21.0), compared with 20.0% (0-55.0) and 1.9 mos (1.7-9.3) in the non-NSMP group (p=0.02). Notably, all responses occurred in the NSMP group. The largest difference was observed between patients with CTNNB1mut with a mPFS of 10.4 months (1.9–NR) compared with 5.2 mos (1.7–9.3) in patients with CTNNB1wt ( p = 0.22). Among 14 patients with LGSOC, the 24-week PFS rate was 71.4% (47.8-95.1), mPFS was 17.5 mos (3.5-NR), DCR was 79% and ORR was 14%, 5 still on treatment at data cut off. The median time on treatment was 10.5 mos (range 1.7-55.4), 4 patients (28%) were on treatment for more than 3 years, the longest still on treatment after 4.6 years. The most common mutation was KRAS in 7 (50%), with no observed differences by KRAS status (KRASmut 11.9 mos [1.9-NR] mPFS, KRASwt 17.5 mos [3.5-NR] mPFS , p=0.89). Despite the 8 patients with HGSOC having CDK4/6 activating mutations the 24-week PFS rate was 12.5% (0-35.4) and the mPFS was 1.6 mos (0.3-1.9). No new safety signals were observed across all subgroups. Conclusions: Abemaciclib demonstrated promising clinical activity in patients with LGSOC regardless of KRASmut status and in ER+ EC, with the greatest activity observed in the NSMP group and potentially CTNNB1-mutated cases; however, these exploratory subgroups need larger validation. Clinical trial information: NCT04469764 .

Use of subtype-specific patterns of clinically relevant antibody–drug conjugate targets in sarcoma to guide precision oncology strategies.

11549 Background: Sarcomas are rare, biologically heterogeneous malignancies with limited targeted treatment options. Antibody–drug conjugates (ADCs) have demonstrated clinical efficacy across multiple solid tumors by exploiting tumor-associated surface antigens; however, their development in sarcoma has been limited by incomplete characterization of ADC target expression across subtypes. We evaluated expression of clinically relevant ADC targets across sarcoma histologies using bulk RNA sequencing and compared these patterns to cancer types with established ADC activity to generate a sarcoma-wide map of ADC target expression. Methods: We analyzed expression of 18 genes encoding cell-surface ADC targets that are FDA-approved or in active clinical development across more than 1,000 sarcoma samples spanning multiple histologic subtypes. Transcriptomic data were derived from The Cancer Genome Atlas (TCGA), an institutional sarcoma registry, and the Oncology Research Information Exchange Network (ORIEN). Per-sample z-scores were generated using pan-cancer distributions to enable standardized comparison. Z-score distributions were summarized using ordinal bins to define target enrichment across sarcoma subtypes. Parallel pan-cancer analyses were performed for contextual comparison. Results: Sarcomas demonstrated heterogeneous but subtype-specific expression of multiple ADC targets across datasets. Several subtypes exhibited elevated expression of select ADC targets, with z-scores comparable to or exceeding those observed in tumor types where ADCs have established clinical activity. ADC targets of particular interest included LRRC15 and CD276 (B7-H3). LRRC15, currently in investigation as an ADC in breast cancer, demonstrated enrichment in sarcoma, with 28% of undifferentiated pleomorphic sarcoma and 38% of dedifferentiated liposarcoma samples exhibiting z-scores > 2, compared to 12% in breast cancer. CD276 similarly showed subtype-specific overexpression across these sarcoma subtypes. No single target was uniformly overexpressed across all sarcomas, underscoring biologic heterogeneity. Pan-cancer comparison revealed that certain sarcoma subtypes ranked among the highest expressors for specific ADC targets. Conclusions: Across a cohort exceeding 1,000 sarcoma patients with diverse histological subtypes, we identify subtype-specific overexpression of multiple clinically relevant ADC targets. This subtype expression map provides a biologic rationale for expanding ADC development into molecularly selected sarcoma subpopulations and supports biomarker-enriched approaches to ADC trial design. Ongoing studies will validate these findings at the protein level using a sarcoma surfaceome approach, including immunohistochemistry and mass spectrometry based profiling.

The trade-offs between efficacy and toxicity: Real-world outcomes of dapsone vs atovaquone for pneumocystis prophylaxis in hematologic malignancies.

e18549 Background: Patients with Hematologic malignancies and multiple myeloma are at increased risk for Pneumocystis jirovecii pneumonia (PJP), necessitating prophylaxis. Dapsone and atovaquone are commonly used alternatives when trimethoprim-sulfamethoxazole is contraindicated; however, comparative real-world data on efficacy and safety remain limited. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, including adults with hematologic malignancies or multiple myeloma who received either dapsone or atovaquone for PJP prophylaxis. Patients with HIV were excluded. Propensity score matching (1:1) was performed to balance demographics, comorbidities among others, yielding 6,187 patients in each cohort. Outcomes assessed over a 180-day follow-up included mortality, PJP, intubation, elevated LDH (≥450 U/L), and treatment-related adverse events including hemolytic anemia, GI upset, rash, transaminitis, and hyperbilirubinemia. Results: After propensity score matching, patients receiving dapsone experienced a significantly lower incidence of PJP compared with those receiving atovaquone. Kaplan–Meier analysis demonstrated a significantly lower hazard of PJP in the dapsone cohort over the 180-day follow-up period (hazard ratio [HR] 0.67, 95% CI 0.52–0.86, log-rank p=0.002). All-cause mortality was significantly lower in the dapsone cohort (HR 0.80, 95% CI 0.74–0.88, log-rank p<0.001). No statistically significant differences were observed between cohorts in the risk of intubation (HR 0.84, 95% CI 0.68–1.03, log-rank p=0.089) or elevated lactate dehydrogenase levels (LDH ≥450 U/L) (HR 0.90, 95% CI 0.78–1.03, log-rank p=0.119).Despite improved efficacy outcomes, our analyses demonstrated higher hazards of several treatment-related adverse events in the dapsone cohort, including gastrointestinal upset (HR 1.32, 95% CI 1.17–1.49; log-rank p<0.001), drug-related rash (HR 1.13, 95% CI 0.99–1.30; log-rank p=0.065), hemolytic anemia (HR 1.30, 95% CI 0.99–1.70; log-rank p=0.055), and hyperbilirubinemia (HR 1.18, 95% CI 1.05–1.33; log-rank p=0.005). In contrast, atovaquone was associated with a significantly higher hazard of transaminitis compared with dapsone (HR 0.54, 95% CI 0.42–0.69; log-rank p<0.001). Conclusions: In this study of patients with hematologic malignancies, dapsone was associated with a significantly lower risk of Pneumocystis jirovecii pneumonia and reduced all-cause mortality compared with atovaquone. However, these benefits were accompanied by higher rates of hematologic, gastrointestinal, and hepatic adverse events. These findings highlight a clinically meaningful trade-off between prophylactic efficacy and tolerability and support individualized selection of PJP prophylaxis.

A prospective, single-arm, single-center observational clinical study on envafolimab (PD-L1 inhibitor) in combination with XELOX for neoadjuvant treatment of locally advanced colon cancer.

e15654 Background: Accumulating evidence supports the application of neoadjuvant chemotherapy for locally advanced colon cancer. The FOxTROT trial has demonstrated the feasibility of oxaliplatin-based neoadjuvant chemotherapy, yet only 8% of patients achieved major pathological response. There is urgent need to explore more effective therapeutic regimens. This study aimed to preliminarily investigate the efficacy and safety of envafolimab combined with XELOX as neoadjuvant therapy for locally advanced colon cancer. Methods: This was a prospective, single-arm, single-center observational clinical study enrolling newly diagnosed patients with locally advanced colon cancer (cT4 N0 M0 or cTx N+ M0). Eligible patients who signed the informed consent received 3 cycles of preoperative neoadjuvant therapy with XELOX (Oxaliplatin 130 mg/m², intravenous infusion, once every 3 weeks; Capecitabine 1000 mg/m², oral administration, once every 3 weeks) plus envafolimab 300 mg, subcutaneous injection, once every 3 weeks. Imaging evaluation was performed after treatment completion, followed by surgical resection. The primary endpoint was the proportion of patients achieving grade 0/1 tumor regression grading (TRG); secondary endpoints included R0 resection rate, pathological complete response (PCR) rate, objective response rate (ORR), disease-free survival (DFS), and safety profile. Results: As of November 28, 2024, a total of 29 eligible patients were enrolled. All 29 patients completed the planned 3 cycles of neoadjuvant therapy, with a 100% full-cycle completion rate (29/29), and the primary endpoint was evaluable in all cases. In the surgical population, 34.5% (10/29) of patients achieved grade 0/1 TRG, the R0 resection rate was 100%, and the PCR rate was 17.2% (5/29). With a median follow-up of 19.7 months (range, 10.2–30.4 months), the DFS rate was 100%. Notably, in the proficient mismatch repair (pMMR) population, the proportion of grade 0/1 TRG was significantly increased to 27.3% (6/22), with a PCR rate of 13.6% (3/22). No patients discontinued treatment due to grade ≥3 treatment-related adverse events. Conclusions: Subcutaneous injection of the anti-PD-L1 monoclonal antibody envafolimab induced significant tumor regression with a favorable safety profile in patients with locally advanced colon cancer. The combination of envafolimab and XELOX yielded encouraging efficacy and a high treatment completion rate. Clinical trial information: NCT05335460 .

Evaluation of a co-designed nurse-led geriatric oncology multidisciplinary model in treatment-naive older adults with solid cancers.

1661 Background: Integration of geriatric assessment into cancer care improves outcomes for older adults but remains limited by resource intensity and reliance on physician time, hence restricting scalability. We evaluated the implementation of a co-created multidisciplinary (MDT) nurse-led geriatric oncology (GO) model developed to address these barriers. Methods: Implementation evaluation was conducted across two tertiary cancer centers. Older adults (≥65 years) with solid cancers underwent nurse-led structured geriatric assessment and MDT review involving medical oncology and geriatric medicine prior to oncology consultation. MDT recommendations addressed identified vulnerabilities, with referral for geriatrician-led CGA reserved for complex cases. Outcomes included G8 screening, referral for CGA, SACT delivery, treatment modification due to frailty, treatment discontinuation, delays, dose modification due to toxicity, and health service utilization (ED, SURC and unplanned hospital admissions within 12 weeks). Demographic and clinical characteristics were summarized using descriptive statistics. Associations with health service use were determined using logistic regression analyses. Results: Of 431 eligible pts, 204 (47.3%) participated in the GO assessment. Median age was 76 years. Most pts had lung cancer (73.1%), followed by GU (14.8%) and upper GI cancers (8.6%). Disease stage did not differ between groups; GO pts were more likely to have ECOG PS 1–2 and 81.4% scored ≤14 on the G8 screening tool. Half (50.7%) were referred for CGA and 67.1% of this cohort received SACT while 32.4% of the cohort not referred for a CGA received SACT. Upfront treatment modification due to frailty was numerically higher in GO pts compared to non-participants (21.1% vs 13.1%, p=0.076). GO participation was associated with higher receipt of SACT (70.6% vs 59.7%, p=0.019), increased use of monotherapy (22.5% vs 13.7%, p=0.016), and lower rates of BSC alone (41.0% vs 59.0%, p=0.033). There were no differences between groups in treatment discontinuation (p=0.64), delays (p=0.074), or dose modifications due to toxicity (p=0.42). GO pts were more likely to be admitted to hospital within 12 weeks of initial oncology consultation. Conclusions: GO assessment supported detailed evaluation of older pts with borderline ECOG PS and increased access to SACT, particularly monotherapy, without increasing treatment-related toxicity. Higher hospitalization rates likely reflect appropriate escalation of care following identification of frailty-related needs. GO vs no GO. GO (n=204) No GO (n=227) p-value Age median (range) 76.0 (72.0, 81.0) 76.0 (71.0, 81.0) 0.77 Monotherapy 46 (22.5%) 31 (13.7%) 0.016 Doublet, or more therapy 98 (48%) 101 (44.5%) 0.46 ED presentation 93 (45.6%) 86 (37.9%) 0.11 SURC use 43 (21.1%) 49 (21.6%) 0.90 Inpatient admission 74 (36.3%) 62 (27.3%) 0.046

Real world efficacy of cetuximab plus chemotherapy as first-line treatment of recurrent and/or metastatic head and neck squamous cell carcinoma.

e18032 Background: Head and neck squamous cell carcinoma (HNSCC) represent a major therapeutic challenge due to its biological heterogeneity and variable prognosis. The use of cetuximab combinations plus chemotherapy has been shown to improve survival outcomes. This study aimed to evaluate the clinical characteristics and the impact of cetuximab-based therapy on overall survival (OS) and progression-free survival (PFS) in patients with recurrent and/or metastatic (R/M) HNSCC. Methods: A retrospective study was conducted including patients diagnosed with R/M HNSCC and treated at the Instituto Nacional de Enfermedades Neoplásicas (INEN) between 2020 and 2024. Clinical variables, response rates, OS, and PFS were analyzed. Survival outcomes were estimated using Kaplan–Meier curves. For survival analysis, patients should receive at least three cycles of cetuximab in combination with chemotherapy. Results: Fifty patients were included, with a median age of 56 years (34% aged >60 years), 54% male, 39% with primary tumors in the oral cavity, and 32% in the oropharynx (19.6% IHC p16-positive). Moderately differentiated carcinoma was the most frequent histology (83.3%). Most patients (80%) had ECOG performance status 1; 34% had a BMI <18, and 78% presented a prognostic nutritional index (PNI) >45. At the start of cetuximab therapy, 38% had systemic disease (14% with concomitant locoregional recurrence), with the lung being the most common metastatic site (94.7%). 80% of patients had received prior treatment: 32.5% radiotherapy alone, 22.5% surgery plus adjuvant radiotherapy, 17.5% surgery plus adjuvant chemoradiotherapy, 17.5% induction chemotherapy followed by radiotherapy alone, 5% induction chemotherapy followed by concurrent chemoradiotherapy, and 5% definitive concurrent chemoradiotherapy. For R/M disease, the most common regimen was cetuximab plus carboplatin and taxanes (60%), followed by the TEPEx regimen (22%). 74% of patients received at least three cycles of chemotherapy. The objective response rate (ORR) was 32.4% (CR = 5.4%, PR = 27%), and the clinical benefit rate (CR + PR + SD) was 70.2%. Maintenance therapy was administered to 51.4% of patients. The median PFS was 6.87 months (5.99-7.74), median OS since initiation of cetuximab was 9.87 months (5.62-14.12), and median OS since initial diagnosis was 22.1 months (19.17-25.03). Conclusions: Cetuximab-based chemotherapy provided meaningful clinical benefit in patients with recurrent and/or metastatic HNSCC, with survival outcomes comparable to those reported in real-world settings. These findings support the continued use of cetuximab in combination regimens as an effective therapeutic option.

Tucatinib (TUC) combined with trastuzumab and pertuzumab (HP) as first-line (1L) maintenance therapy for HER2+ metastatic breast cancer (MBC): An in-depth safety analysis of HER2CLIMB-05.

1042 Background: The primary analysis of the phase 3 HER2CLIMB-05 study (NCT05132582) showed the addition of TUC to 1L maintenance HP yielded a statistically significant improvement in progression-free survival (per investigator) versus control treatment (hazard ratio: 0.641, P < 0.0001) in patients with HER2+ MBC. Here we report our findings from an in-depth safety analysis of HER2CLIMB-05. Methods: Patients with centrally confirmed HER2+ MBC without evidence of progression following chemotherapy-based induction treatment (taxane + HP) were randomly assigned 1:1 to TUC (300 mg) or placebo (PBO) BID, both in combination with HP. The safety analysis set included all randomly assigned patients who received ≥1 dose of any study treatment. Treatment-emergent adverse events (TEAEs), laboratory values, and TUC/PBO dose modifications and discontinuations were examined. Results: Among patients in the safety analysis set (TUC arm = 326; PBO arm = 324), median treatment durations of TUC and PBO were 17.1 months (range: 0.4–36.5) and 15.5 months (range: 0.5–41.3), respectively. Grade (G) ≥3 TEAEs occurred in 42.3% of patients in the TUC arm and 24.4% in the PBO arm; the most frequent G ≥3 TEAEs in the TUC arm were elevated alanine aminotransferase (ALT; 13.5%) and aspartate aminotransferase (AST; 7.1%). TUC was discontinued in 13.5% of patients due to a TEAE. Cardiac TEAEs were similar between TUC and PBO arms (4.3% vs 6.2%). TEAEs of hepatic events (43.6% vs 15.7%) and diarrhea (72.7% vs 51.2%) occurred at higher incidence in the TUC arm versus the PBO arm (Table). In the TUC arm, increased ALT (28.2%) and AST (25.8%) accounted for the majority of hepatic TEAEs. Most hepatic and diarrhea TEAEs were managed with TUC dose modifications and/or discontinuation; 7.7% of patients discontinued TUC due to hepatic TEAEs and 1.5% discontinued due to diarrhea (Table). Among the patients with a TEAE of diarrhea, 57.7% and 29.9%, respectively, in the TUC and PBO arms used antidiarrheals; the most used medication was loperamide. Further details of the in-depth safety analysis will be presented. Conclusions: TUC addition to 1L HP maintenance therapy may be an effective option for HER2+ MBC with a clinically manageable safety profile. Clinical trial information: NCT05132582 . TEAEs* Any Any hepatic Increased ALT/AST Diarrhea Arm TUC PBO TUC PBO TUC PBO TUC PBO Any G, % 99.1 96.6 43.6 15.7 28.2/25.8 7.1/9.0 72.7 51.2 G ≥3 42.3 24.4 18.1 1.2 13.5/7.1 0.6/0.6 6.1 4.0 Any G: Median time to onset (days) 34.5 85.0 11.0 32.0 Median time to resolution (days) 25.0 22.0 2.0 5.0 Any G: TUC/PBO dose hold, % 49.4 25.3 19.3 2.5 12.6/4.0 0.6/0.6 8.6 3.4 TUC/PBO dose reduction, % 29.1 11.1 16.3 0.9 11.7/2.8 0.3/0.6 6.4 3.1 TUC/PBO discontinuation, % 13.5 2.2 7.7 0 4.0/0.3 0/0 1.5 0.9 *As of data cutoff, Sep 5, 2025.

Matching-adjusted indirect comparison (MAIC) for belantamab mafodotin (belamaf) with pomalidomide and dexamethasone (BPd) vs daratumumab with pomalidomide and dexamethasone (DPd) in relapsed/refractory multiple myeloma (RRMM).

e19574 Background: BPd is approved for patients (pts) with RRMM in multiple countries based on results of the phase 3 DREAMM-8 trial. DREAMM-8 evaluated BPd vs pomalidomide with bortezomib and dexamethasone, allowing enrollment of pts previously treated with daratumumab. To support clinical decision-making in the absence of head-to-head comparison, a MAIC was performed to estimate the relative clinical efficacy of BPd vs DPd in pts with RRMM who received ≥1 prior therapy line (2L+), including lenalidomide (len). Methods: A systematic literature review was undertaken and updated as of January 2024 to identify efficacy/safety data in 2L+ RRMM, and studies were assessed for common treatment arms and pt characteristics. MAICs of progression-free survival (PFS) and minimal residual disease negativity (MRD-) were conducted using the len-exposed populations from phase 3 trials of BPd (DREAMM-8) and DPd (APOLLO). As these trials lack a common comparator arm, an unanchored approach was required. Individual pt data (IPD) were available for BPd-treated pts (n=155) from DREAMM-8, while only published summary data were available for DPd-treated pts (n=151) from APOLLO. BPd-treated pts from DREAMM-8 were weighted (using IPD) to match DPd-treated pts from APOLLO in terms of age (<75 , ≥75 years), prior lines of therapy (LOT; 1, 2–3, ≥4), refractoriness to len/immunomodulatory drugs (IMD; yes, no), refractoriness to proteasome inhibitors (PI; yes, no), International Staging System (ISS) stage (1/2, 3), cytogenetic risk (standard, high), Eastern Cooperative Oncology Group performance status (ECOG PS; 0, 1, 2), and creatinine clearance (CrCl; ≤60, >60 mL/min). Outcomes for weighted BPd-treated pts were compared to those for DPd-treated pts. DREAMM-8 interim analysis 1 (MRD-) and 3 (PFS) data were used for analysis. Cox regression and logistic regression were performed for PFS and MRD- comparisons, respectively. Results: After matching, equal proportions in both arms were: ≥75 years (17%); had 2–3 prior LOT (75%); were refractory to an IMD (79%) or PI (47%); had ISS stage 3 (22%); ECOG PS of 1 (36%); had CrCl ≤60 mL/min (26%); and had high cytogenetic risk (38%). Effective sample size of weighted BPd-treated pts was 65.6. PFS favored BPd, with medians of 18.1 vs 12.4 months (hazard ratio 0.74 [95% confidence interval 0.50, 1.09]). MRD- also favored BPd, with rates of 25.8% vs 8.6% (odds ratio 2.73 [95% confidence interval 1.26, 5.92]). Only MRD- was statistically significant. Conclusions: While MAICs have inherent limitations, BPd demonstrated improved relative clinical efficacy vs DPd when adjusting for differences in key baseline pt characteristics. These findings demonstrate the importance and utility of BPd in the 2L+ RRMM setting with the growing use of len with daratumumab in early LOT.

Osimertinib in the treatment of EGFR mutation–positive advanced non-small cell lung cancer: A meta-analysis.

e20723 Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used for the treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). This meta-analysis systematically reviews the evidence on the effectiveness and safety of osimertinib in treating advanced non-small cell lung cancer with EGFR mutations. Methods: Following PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov from inception to July 2025. Randomized controlled studies that reported the efficacy and safety of osimertinib versus other treatments (chemotherapy, other EGFR-TKIs, etc.) in treating EGFR-mutated NSCLC were included. Data analysis was performed using RevMan 5.4, with risk ratios (RRs) and 95% confidence intervals (CIs) calculated for dichotomous outcomes using a random-effects model. Risk of bias was assessed using the Cochrane RoB 2.0 tool. The primary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The additional outcome was the incidence of adverse events. Results: A total of 23 RCTs involving 7,525 participants were included. Among them, 4,061 participants were in the osimertinib group, while 3,444 were in the standard treatment group. Meta-analysis indicated that PFS (RR 0.74, 95% CI, 0.58–0.95, p = 0.02, I² = 94%) and OS (RR 0.81, 95% CI, 0.70–0.94, p = 0.006, I² = 72%) in the experimental group were statistically significant compared to the control group. ORR (RR 1.36, 95% CI, 1.14–1.62, p = 0.0005, I² = 93%) and DCR (RR 1.13, 95% CI, 1.04–1.22, p = 0.004, I² = 90%) also yielded statistically significant results but favored the control group. Among the reported adverse events, the experimental group showed a statistically significant reduction in the incidence of nausea (RR 0.51, 95% CI, 0.31–0.83, p = 0.007, I² = 80%) and vomiting (RR 0.34, 95% CI, 0.14–0.79, p = 0.01, I² = 78%) compared to the control group. The control group showed a statistically significant reduction in diarrhoea (RR 1.30, 95% CI, 1.02–1.65, p = 0.03, I² = 80%). The incidence of fatigue, rash, and loss of appetite favored the experimental group, but the results were insignificant. The incidence of URTI, rash, and stomatitis was higher in the control group, but the reduction was statistically insignificant. Conclusions: This meta-analysis suggests that osimertinib is an effective and well-tolerated treatment strategy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. This meta-analysis has several limitations, including heterogeneity among included studies, potential publication bias, and variability in study quality and sample sizes.