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Cross-continent inter-laboratory transfer of a clinical mass spectrometry lectin magnetic bead assay (LeMBA-MS) for ovarian cancer serum glycoprotein biomarkers.
e17586 Background: Accurate non-invasive detection of ovarian cancer can assist in pre-surgical triaging and screening for earlier diagnosis and better survival from ovarian cancer. Lectin magnetic bead-coupled mass spectrometry (LeMBA-MS) was used to discover ovarian cancer biomarkers using biobank samples from the UK and validated in a cohort from Australia (Dutt et al. 2023 Proteomics Clinical Applications 17(4):e2200114). This study evaluates LeMBA-MS as a clinical assay platform by determining its inter-laboratory transfer, robustness and reproducibility across reference serum and clinical samples. Methods: Proseek Bio prepared LeMBA processing reagents, which were shipped from Australia to Arcadia Life Sciences in Malaysia for this study. A dynamic multiple reaction monitoring (dMRM) method was transferred electronically. The study comprised three phases. Firstly, the dMRM method was implemented and optimized at Arcadia using a direct serum tryptic digest of a commercial serum. Then, the reference serum was processed using Proseek Bio reagent kit and reproducibility analyzed across 5 replicate runs, with 15% CV for 90% of the peptides as acceptance for reproducibility. Finally, ten Malaysian clinical serum samples (NMRR-18-544-40614), comprising five epithelial ovarian cancer and five benign cases, collected prior to treatment, were analyzed in triplicate. Results: All three phases of the study were successfully completed with minor adjustments and remote consultation. Two batches of lectin-beads were produced and post-shipment performance monitored using a standard protein showed no significant differences for all three peptides (t-test p > 0.18). The implemented dMRM method comprised 94 biomarkers and 6 control peptides. The pre-defined biomarker peptide reproducibility criteria were met for both the reference serum and the clinical samples: 85 biomarker peptides (90.4%) had CVs below 15%, while 9 (9.6%) exceeded 15%. The latter corresponded to low-abundance peptides, and will likely be removed from further development. Statistical analysis on the small independent dataset showed 28 peptides from 8 glycoproteins to be significantly different (adjusted p-value <0.05) between benign and epithelial ovarian cancer groups, with 25 peptides lower in cancer compared to benign. A principal component analysis plot showed clear separation of the groups. Conclusions: This inter-laboratory study demonstrates the robustness of LeMBA-MS as a suitable clinical assay format, and provides pilot independent clinical validation of candidate ovarian cancer biomarkers. Additional clinical validation studies in diverse populations are warranted to inform biomarker panel development.
Racial variation in pain medication prescriptions among breast, prostate, and pancreatic cancer patients treated in a large community oncology setting.
1650 Background: Patients (pts) from racially and ethnically minoritized populations are less likely to receive opioid analgesics for cancer-related pain, raising concern for inequitable symptom management. Although guidelines support opioid therapy within a multimodal approach, large scale evidence on racial differences in pain medication use across cancer types remains limited. This study uses real-world data from a large community oncology network to evaluate prescribing patterns of pain medication among high prevalence and high pain burden cancers by race and cancer type. Methods: Electronic medical record data from The US Oncology Network identified pts diagnosed with breast, prostate, or pancreatic cancer between January 2021 and June 2025, followed through December 2025. Pain medication (acetaminophen, NSAID, opioid) prescriptions and median time from cancer diagnosis to pain medication prescription were described. Strong opioids were defined as fentanyl, hydromorphone, morphine, or oxycodone, while general opioid use included hydrocodone and tramadol. Results: Among breast cancer patients overall (58,308 White; 7,705 Black; 3,652 Asian), pain treatment was received by 19% of White pts and by 24% of both Black and Asian pts, with median time to first pain medication shortest for White patients (65 d) and longest for Black patients (80 d). Prescriptions for strong opioids for breast cancer were lowest among Asian patients (28%), compared to 32% in Black patients and 35% in White patients. Among prostate cancer overall (19,268 White; 3,385 Black; 469 Asian), where receipt of pain medication was 17%, 20%, and 15%, respectively, Asian pts experienced the longest time to pain medication (86 d) versus the shortest among White patients (50 d). Asian patients had the fewest prescriptions for strong opioids (28%) compared with Black (54%) and White patients (50%). In pancreatic cancer (7,972 White; 1,035 Black; 330 Asian), pain medication prescriptions overall (52%, 55%, 50%, respectively) and for strong opioids (71%, 68%, 73%, respectively) were comparable across racial groups, and median time to pain medication showed minimal variation (18–22 d). Conclusions: In this large, nationally representative community oncology population, clinically meaningful racial differences in time to pain medication initiation and strong opioid prescribing were observed for breast and prostate cancer but not pancreatic cancer. Minoritized populations experienced delays in pain management, and Asian patients consistently received fewer strong opioid prescriptions. These results highlight that inequities in pain management vary across malignancies, and categories of pain medication. These findings underscore the need for culturally informed, cancer specific interventions to promote equitable symptom management.
Sociodemographic determinants of end-of-life care settings and place of death among patients with lung cancer in the United States.
12077 Background: Optimizing the place of death is a key component of quality end-of-life (EOL) cancer care, with home and hospice settings generally preferred over acute care hospitals. While lung cancer mortality has declined, disparities in EOL care utilization remain a concern. This study utilized the CDC WONDER database to analyze longitudinal trends and sociodemographic predictors of place of death for lung cancer decedents over a 25-year period. Methods: We performed a retrospective analysis of death certificate data for all lung cancer-related deaths in the U.S. from 1999 to 2023. Place of death was categorized as Decedent’s Home, Hospice/Nursing Facility, Medical Facility-Inpatient (referent), or Outpatient/ER. Multinomial logistic regression estimated adjusted odds ratios (aOR) with 95% confidence intervals (CI) for predictors, adjusting for age, sex, race, ethnicity, urbanization, and year. Results: A total of 3,563,902 lung cancer deaths were identified. The most common place of death was the decedent's home (44.9%), followed by inpatient medical facilities (30.7%) and hospice/nursing facilities (22.1%). There was a significant longitudinal shift away from inpatient death. For every advancing calendar year, the odds of dying at home increased by 3% (OR 1.03; 95% CI 1.03-1.03) and the odds of dying in a hospice/nursing facility increased by 4% (OR 1.04; 95% CI 1.04-1.04). Compared to White patients, Black patients had significantly lower odds of dying at home (OR 0.57; 95% CI 0.57-0.58) or in a hospice facility (OR 0.68; 95% CI 0.68-0.68). Notably, Black patients had 53% higher odds of dying in an Outpatient/ER setting (OR 1.53; 95% CI 1.53-1.53) compared to White patients. Patients in rural areas had higher odds of dying at home (OR 1.17; 95% CI 1.16-1.17) but lower odds of dying in a hospice/nursing facility (OR 0.93; 95% CI 0.92-0.93) compared to those in large metropolitan areas. Conclusions: From 1999 to 2023, lung cancer mortality shifted significantly from inpatient settings to home and hospice care. Yet, Black patients remain significantly less likely to utilize home/hospice care and more likely to die in acute ER settings. Additionally, rural patients show high home death rates but lower facility-based hospice use, suggesting infrastructure gaps. Targeted interventions are required to ensure equitable EOL care access.
A phase 2 double-blind, randomized, prospective, placebo-controlled study of NanO₂ combined with radiation and temozolomide in patients with newly diagnosed glioblastoma: RESTORE.
2065 Background: Glioblastoma (GBM) contains extensive hypoxic regions due to tumor-associated thrombosis and abnormal vasculature. Hypoxia drives resistance to radiation (RT) and temozolomide (TMZ) by limiting oxygen-dependent DNA damage, enabling DNA repair, and reducing drug efficacy and delivery. The RESTORE trial (NCT03862430) is the first randomized, prospective, placebo-controlled study of NanO₂ (2% w/v dodecafluoropentane emulsion) in GBM, a fluorocarbon-based oxygen therapeutic hypothesized to reoxygenate hypoxic GBM tissue, with the goal of enhancing the efficacy of chemoradiation. Methods: Patients with newly diagnosed GBM (WHO 2021) received standard-of-care radiation (60 Gy) with concurrent TMZ (75 mg/m²/day). Patients were randomized 2:1 to receive either NanO 2 or 0.9% sodium chloride administered intravenously immediately prior to each RT fraction, with continuous supplemental oxygen given during the infusion and RT. Following chemoradiation, patients completed a four-week recovery period before initiating adjuvant TMZ for 6 cycles. The primary endpoint is progression free survival and secondary endpoints include overall survival, objective response rate, pseudoprogression rate, and patient reported outcomes. Results: Between May 2023 and October 2025, 93 patients were treated (safety set). The study has completed the planned enrollment. Median age was 63 years (range, 19–84) and 57% were men. As of the data cutoff on 12/29/25, all patients completed the follow up visit 4 weeks after chemoradiation. Sixty-eight patients (73%) remained on study undergoing adjuvant TMZ or in long-term follow-up. Twenty-one patients passed of tumor progression and 4 patients withdrew consent. The median duration on study was 8.7 months (range, 1.3–31.4). During chemoradiation and the four-week recovery, 63 treatment-emergent adverse events (TEAEs) of CTCAE severity grade ≥3 were reported in 37% of patients, with brain edema, lymphocyte count decreased, and platelet count decreased being the most frequently reported. Twenty-six treatment-emergent serious adverse events (TESAEs) occurred in 19% of patients, with embolism, pulmonary embolism, and seizure being the most frequently reported. Three TESAEs were assessed as possibly or probably related to study drug; none were unexpected. Survival follow up is ongoing. Conclusions: In this blinded, pooled safety analysis of a randomized phase 2 trial in newly diagnosed GBM, the study treatment was well tolerated and no new safety signals were identified. Treatment allocation remains blinded. Efficacy outcomes and arm-specific safety analyses will be reported after completion of the primary endpoint analysis. Clinical trial information: NCT03862430 .
Phase I pharmacokinetic study of high-dose vitamin C dosing regimens in patients with advanced hepatobiliary-pancreatic cancers.
e15133 Background: High-dose vitamin C (HDVC) has demonstrated synergistic or sensitizing effects with chemotherapy and radiotherapy in preclinical studies. However, its clinical translation has been largely limited due to suboptimal pharmacokinetics, characterized by a short half-life and insufficient duration of effective plasma concentration. To investigate whether optimizing the dosing regimen can prolong the maintenance of effective plasma vitamin C concentrations in patients with advanced hepatobiliary and pancreatic malignancies, thereby providing a new strategy to enhance its clinical antitumor effects. Methods: 18 patients with advanced hepatobiliary and pancreatic malignancies were enrolled and assigned to three dosing cohorts: Cohort A (0.5 g/kg once daily, qd), Cohort B (0.5 g/kg every 12 hours, q12h), and Cohort C (0.75 g/kg every 12 hours, q12h), with 6 patients in each group. All patients received standard antitumor therapy concurrently with HDVC, administered via a central venous catheter for 7 consecutive days. Plasma vitamin C concentrations were measured by high-performance liquid chromatography (HPLC) at fixed time points daily. Results: No significant differences in baseline plasma vitamin C concentrations were observed among the three cohorts. Compared with the once-daily regimen (0.5 g/kg qd), the every-12-hour regimen (0.5 g/kg q12h) significantly enhanced the maintenance level of plasma vitamin C concentration. However, increasing the dose to 0.75 g/kg q12h did not further elevate the plasma concentration. Regarding safety, only one patient experienced nausea and discomfort, with no other significant adverse events observed. Conclusions: In patients with advanced hepatobiliary and pancreatic malignancies, increasing the dosing frequency (e.g., to every 12 hours) under the same total daily dose can more effectively maintain the plasma concentration of HDVC with a favorable safety profile. This provides a feasible dosing optimization approach to potentially improve its antitumor efficacy. A further dose increase to 0.75 g/kg q12h did not demonstrate additional pharmacokinetic benefits in this study. Clinical trial information: NCT07121036 .
Keratin 19 (KRT19) as a circulating biomarker to measure disease burden and guide treatment in urothelial cancer.
4591 Background: Circulating tumor DNA (ctDNA) has emerged as a valuable biomarker in urothelial cancer but remains limited by cost and turnaround time. Keratin 19 (KRT19) is a cytoskeletal protein that is highly and specifically expressed in urothelial tumor tissue in The Cancer Genome Atlas (TCGA) urothelial cancer cohort. Based on this tumor specific expression, we hypothesized that circulating KRT19 levels could serve as a rapid, inexpensive measure of disease burden to guide systemic therapy for urothelial cancer. Methods: Two patient cohorts from completed clinical trials were analyzed. HCRN GU16-257, a phase 2 trial of gemcitabine, cisplatin, and nivolumab as organ-sparing treatment for localized muscle-invasive bladder cancer, included 76 patients evaluable for KRT19 with median follow-up of 30 months. HCRN GU14-182, a phase 2 switch maintenance trial of pembrolizumab versus placebo following first-line chemotherapy for metastatic urothelial cancer, included 46 patients evaluable for KRT19 in the pembrolizumab arm with median follow-up of 12.9 months. Serum KRT19 levels were quantified using Olink proteomics technology alongside 91 additional proteins. Cox proportional hazards models assessed associations between KRT19 expression and clinical outcomes, with adjustment for multiple comparisons using false discovery rate correction. Results: In the GU16-257 cohort, among 92 peripheral blood analytes tested at baseline (C1D1), KRT19 demonstrated the strongest association with overall survival. Elevated baseline KRT19 was independently associated with inferior overall survival (HR 2.62, adjusted p=0.016) and metastasis-free survival (HR 3.01, adjusted p=0.001). A decrease in KRT19 from C1D1 to C3D1 was associated with improved overall survival (HR 0.59, unadjusted p=0.024) and metastasis-free survival (HR 0.60, unadjusted p=0.041). In GU14-182, elevated baseline KRT19 was associated with inferior overall survival (HR 2.11, adjusted p=0.034) and progression-free survival (HR 1.57, unadjusted p=0.024). Optimal KRT19 cutpoints enabled significant risk stratification for mortality and disease progression in both cohorts. Analysis of an independent peripheral blood single-cell RNA sequencing cohort from patients with urothelial cancer confirmed epithelial cells as the predominant source of circulating KRT19. Conclusions: KRT19 represents a promising, readily measurable serum biomarker with specificity for urothelial cancer. Both baseline levels and on-treatment changes correlate with disease progression and survival. Further validation of KRT19 as a tool to assess disease burden and guide treatment decisions in urothelial cancer is warranted.
Antibody-drug conjugate (ADC) biomarker targets in endometrial cancer (EC): Molecular characterization and implications for therapeutic decision-making.
5616 Background: Given the evolving landscape of ADCs, we evaluated expression of emerging ADC targets in EC and compared expression patterns across molecular subgroups (POLE mutated [POLEm], MSI-high [MSI-H], TP53-mutated [TP53m] or No Specific Molecular Profile [NSMP]) defined by the Proactive Molecular Risk Classifier for Endometrial Cancer. Methods: Tumors were analyzed by DNA and RNA sequencing and immunohistochemistry (IHC) for select proteins (Caris Life Sciences, Phx, AZ). ER+ defined as % staining ≥ 1%. Statistics were calculated by Mann-Whitney U test and adjusted for multiple comparisons (q < 0.05). Expression was split into top quartile ( H ) and bottom quartile ( L ). Overall survival (OS) was obtained from insurance claims data and calculated from first treatment to last contact. Hazard ratios (HR) were calculated by Cox proportional hazards with p-values by log-rank tests. Results: Of 13,731 EC samples, 2.4% (n=335) were POLEm, 21.6% (n=2,961) MSI-H, 46.8% (n=6,420) TP53m and 29.2% (n=4,015) NSMP. HER2+ by IHC was highest in TP53m tumors compared to POLEm, MSI-H, and NSMP (15.9% vs 1.2% vs 0.8% vs 4.0%; p<0.05). TP53m tumors had the highest RNA expression of CDH6, B7-H4, CLDN6, ERBB3, ERBB2, FOLR1, NECTIN2, NECTIN3, and TF; NSMP tumors had the highest expression of TROP2 and NECTIN4 relative to other subtypes (Table 1). Compared to all solid tumors, TP53m EC had the highest median RNA expression of B7-H4 and second highest of CLDN6 and FOLR1. Assessing the prognostic effect of ADC targets by subtype, POLEm CLDN6 H tumors had improved OS compared to CLDN6 L (HR 0.39, p=0.003). In MSI-H tumors, TROP2 H , CDH6 H , B7-H4 H , CLDN6 H , ERBB3 H , ERBB2 H , FOLR1 H and NECTIN2-4 H was associated with improved OS (HR 0.57-0.84, p<0.05). In TP53m tumors, TROP2 H , B7-H4 H , FOLR1 H , HER3 H , and NECTIN4 H was associated with improved OS (HR: 0.75-0.80, p<0.05) and NECTIN1 H and B7-H3 H with worse OS (HR: 1.26, p<0.001). In ER- NSMP tumors (n=804), B7-H4 H , ERBB3 H , ERBB2 H and NECTIN4 H had improved OS (HR: 0.62-0.74, p<0.05) and B7-H3 H and NECTIN1 H had worse OS (HR: 1.40, p=0.01). In ER+ NSMP tumors (n=2,896), TROP2 H and TF H had improved OS (HR: 0.73-0.82, p<0.05) and ERBB2 H and CDH6 H had worse OS (HR: 1.24-1.29, p<0.05). Conclusions: Expression of ADC targets differs by molecular subtype with varying associations with OS in EC patients. Focusing future clinical trials on EC subsets with high biomarker expression will be critical to efficiently developing novel targeted therapeutics. RNA expression by subtype (transcripts per million). Subtype B7-H3 B7-H4 CD276 CLDN6 ERBB2 ERBB3 FOLR α NECTIN1 NECTIN2 NECTIN3 NECTIN4 TF TROP2 POLEm 10.0 10.0 24.9 0.38 25.6 52.7 7.6 7.2 14.9 15.0 5.6 0.70 58.2 MSI-H 5.8 12.0 23.2 0.32 23.3 58.9 8.6 7.8 14.7 13.6 9.7 0.84 61.1 TP53m 21.5 15.8 22.0 2.90 32.8 62.4 20.7 6.0 18.6 18.6 7.1 0.98 54.8 NSMP 7.5 14.0 22.3 0.35 25.1 56.2 10.3 6.6 14.9 11.5 10.5 0.78 81.8
Impact of adjuvant immunotherapy on stage III acral malignant melanoma (ALM) in a Peruvian cancer center: A real-world experience.
e21541 Background: Acral malignant melanoma (AMM) is an aggressive and distinct subtype of melanoma associated with poor prognosis and reduced response to immunotherapy. Peru shows a high incidence of the acral subtype (~60%), similar to that reported in Asian populations. This study aimed to evaluate the clinical benefit of adjuvant immunotherapy with pembrolizumab in Peruvian patients with clinical stage III melanoma, with a focus on the acral subtype. Methods: A retrospective descriptive analysis was conducted in patients with clinical stage III malignant melanoma treated between 2021 and 2024. Clinicopathological data were obtained from medical records. Baseline characteristics were compared between acral and non-acral melanoma patients. Efficacy was assessed using recurrence-free survival (RFS). Statistical significance was set at p<0.05 using SPSS software. Survival curves were estimated using the Kaplan–Meier method. Results: A total of 48 patients were included. Median age was 59 years (range 27–83), and 94% had an ECOG performance status of 0–1. The most common primary site was the lower extremities (58%). Most patients presented with T4b tumors (65%, median Breslow thickness 7 mm), N1a disease (23%), and stage IIIC (65%) according to the AJCC 8th edition. The acral subtype accounted for 42% of cases. All patients received adjuvant anti-PD-1 therapy (pembrolizumab), and 19% also received radiotherapy. Male sex, presence of microsatellite disease, and higher nodal involvement were more frequent in acral compared with non-acral melanoma. After a median follow-up of 24 months, estimated 1-year RFS was 78% in non-acral patients and 69% in acral patients (p=0.86). Conclusions: This single-center study reports a high incidence of acral malignant melanoma among Peruvian patients with stage III disease. Clinical characteristics, 1-year RFS, and recurrence patterns were comparable between acral and non-acral subtypes. Adjuvant immunotherapy with pembrolizumab demonstrated clinical benefit in Peruvian patients with acral melanoma.
Association of the 70-gene assay and homologous recombination deficiency in patients with high risk 2 breast cancers.
561 Background: Homologous recombination deficiency (HRD) is a biomarker for impaired DNA repair proficiency and genomic instability, associated with sensitivity to DNA-damaging agents. MammaPrint (MP), a 70-gene assay, stratifies early breast cancer (EBC) by UltraLow, Low, High Risk 1 (H1) or High Risk 2 (H2) of recurrence. Compared to patients (pts) with H1 tumors, pts with H2 tumors derive greater benefit from anthracycline-based chemotherapy. Here we analyze HRD signatures to assess whether MP gene expression profiling may detect pathway activity in H2 tumors indicating DNA repair deficiency. Methods: We analyzed tumors from pts enrolled in the FLEX study who consented to full transcriptome and clinical data collection, with available MP and BluePrint (BP; Luminal or Basal) results (N=1298). HRD status assessed using a 228-gene signature was further refined into a 26-gene panel (Jacobson et al., 2023). The R-package Limma was used to preprocess gene expression data. For each gene, the median expression value of probes mapping to the gene was calculated. Differences in HRD scores were compared across MP and BP groups using a t-test. Results: Pts with HR+HER2- EBC HRD scores differed significantly by both MP and BP. Using the 228-gene HRD signature, H2 tumors were associated with higher HRD compared with H1 cancers (p<0.001). Luminal H2 tumors were also associated with higher HRD scores than Luminal H1 tumors (p<0.001). Basal tumors were associated with higher HRD compared with Luminal tumors within both H1 and H2 (Luminal H1 vs Basal H1 and Luminal H2 vs Basal H2; both p<0.001), and Basal H2 tumors had higher HRD scores than Basal H1 tumors (p<0.001). Similar patterns were observed within the 26-gene HRD panel. H2 tumors were associated with higher scores than MP H1 tumors (p<0.001), and Luminal H2 tumors were associated with higher scores than Luminal H1 tumors (p<0.001). Basal tumors were associated with higher HRD than Luminal tumors within both MP risk groups (Luminal H1 vs Basal H1, p=0.002; Luminal H2 vs Basal H2, p<0.001). Basal H2 tumors demonstrated numerically higher scores than Basal H1 tumors using the 26-gene panel, but did not reach statistical significance (p=0.062). Conclusions: In this real-world analysis, MP and BP identified differences in underlying HRD biology, with H2 tumors enriched for HRD and Luminal H1 tumors demonstrating relative homologous recombination proficiency. These findings may provide a biological rationale for the anthracycline chemotherapy and immunotherapy benefit observed in pts with H2 tumors and further evidence for MP as a tool for refined therapy selection. Additional research is warranted to examine MP as a biomarker for HRD-sensitive therapies such as PARP inhibitors and carboplatin. These results further highlight biological diversity within genomically high-risk tumors, uniquely detected by MP and BP. Clinical trial information: NCT03053193 .
Mechanistic evaluation of thymol in a rat model of methotrexate-induced intestinal injury: NF-κB, Nrf2/HO-1, PPARγ/SIRT1, and RIPK1/RIPK3/MLKL pathways.
e24172 Background: Thymol is a monoterpene phenol with numerous pharmacological properties, including antibacterial, antitumor, anti-inflammatory, antidiabetic, antioxidant, and antirheumatic activities. The study was designed to explore the potential of thymol to protect against methotrexate (MTX)-induced intestinal injury in rats and to explore the associated molecular mechanisms. Methods: Rats were randomly allocated into five groups: Control, thymol (100mg/kg, p.o, for 10 days), MTX (20 mg/kg; i.p. single dose on day 5), thymol (60mg/kg, p.o, for 10 days) + MTX and thymol (100mg/kg, p.o, for 10 days) + MTX. Results: Thymol administration attenuated MTx-induced severe histological alterations and restored the architecture of intestinal villi and crypts. In addition, thymol significantly reduced intestinal oxidative damage by reducing lipid peroxidation and elevating superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as enhancing intestinal protein expression of Nrf2/HO-1, PPAR-γ, and SIRT1. Furthermore, thymol markedly reduced MTX-induced intestinal inflammation by decreasing IL-6 and TNF-α levels, which was associated with inhibition of NF-κB p65 activation. Moreover, thymol effectively inhibited necroptotic signaling in the intestine through downregulation of RIPK1/RIPK3/MLKL signaling and counteracted apoptosis via reduced cleaved caspase-3 and caspase-8 protein expression. Conclusions: Thymol may present a promising strategy for mitigating MTX-induced intestinal toxicity by exerting potent antioxidant, anti-inflammatory, and anti-necroptotic effects potentially mediated by modulating NF-κB p65, Nrf2/HO-1, PPAR-γ/SIRT1, RIPK1/RIPK3/MLKL signaling, and apoptosis.
Postoperative adjuvant therapy of donafenib in hepatocellular carcinoma with high-risk recurrence factors: A real world, prospective, observational study.
e16268 Background: The five-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection is as high as 70% and remains a major clinical challenge. The efficacy and optimal implementation of adjuvant therapies after hepatectomy still need further validation. Donafenib has been approved as a standard treatment for patients with unresectable HCC in China. Here, we describe our preliminary results regarding the efficacy and safety of donafenib as an adjuvant therapy for patients with HCC after hepatectomy. Methods: This was an observational study of patients with HCC following hepatectomy treated with donafenib in routine practice at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The enrolled patients were 75 years or younger, had been diagnosed with HCC, showed no evidence of recurrence at radiological follow-up within one month after hepatectomy, and had at least one high recurrence risk factor, such as tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion, or serum a-fetoprotein level before surgery ≥400 ng/mL. All of the patients had adequate hematologic, hepatic, and renal function. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included 6- and 12-month RFS rates, overall survival, and adverse events. Results: 52 patients were enrolled in this study. The median age was 56 years (range, 30–72), 88.5% were males, 82.7% with HBV, 26.9% had preoperative serum a-fetoprotein levels ≥400 ng/mL, 31.9% had tumor diameters ≥5 cm, 38.5% had tumor numbers ≥2, and 36.5% had microvascular invasion. The median follow-up time for the entire patient cohort was 36.1 months (95% confidence interval [CI], 32.3–39.9), and 20 of 52 patients relapsed, with a recurrence rate of 38.5%. The median RFS was not reached; the 6-, 12- and 24-month RFS rates were 92.2%, 76.4% and 65.4%, respectively. And the median OS was not reached, either; the 6-, 12- and 24-month OS rates were 100%, 98% and 93%, respectively. Treatment-related adverse events (TRAEs) occurred in 84.6% of the patients, most of which were grades 1–2. Grade 3/4 TRAEs, including hand-foot syndrome, liver damage and severe rash, were observed in 13 (25%) patients. No grade 5 TRAEs occurred. Conclusions: The findings of the present study suggest that donafenib as adjuvant therapy may be a potentially effective way to prevent HCC recurrence after curative surgery. Our findings should be validated in a larger, prospectively evaluated sample. Clinical trial information: ChiCTR2200064030.
Diagnostic yield after pre-biopsy steroid administration in primary CNS high-grade B-cell lymphoma.
7056 Background: Primary central nervous system high-grade B-cell lymphoma (PCNSL) is typically diagnosed via brain biopsy. Corticosteroids are often administered pre-biopsy to reduce vasogenic edema, but are hypothesized to decrease diagnostic yield by inducing lymphocyte apoptosis. This study aims to evaluate whether steroid administration prior to biopsy affects the likelihood of obtaining a diagnostic result in pts with PCNSL. Methods: A retrospective chart review of Brown University Health pts (2015-2024) with PCNSL, including primary CNS diffuse large B cell lymphoma (DLBCL), was conducted. Collected variables included demographics (age, sex, ECOG), steroid dose, biopsy type (excisional, incisional, or stereotactic needle biopsy) and outcome of biopsy (diagnostic vs. undiagnostic). Statistical analysis comparing pre-biopsy steroid (PBS) group with steroid naive group was conducted using Chi-squared, Wilcoxon rank sum and Fisher’s Exact test. Results: A total of 59 pts were found to have biopsy proven PCNSL and were included in statistical analysis. 53 pts had DLBCL and 6 had high grade PCNSL. Baseline demographics and biopsy types did not significantly differ between PBS group and steroid-naive pts (p>0.05). Among pts that received PBS, 35/35 (100%) had a diagnostic biopsy compared with 22/24 (92%) in pts who did not receive steroids. Pre-biopsy steroid use was not associated with a statistically significant difference in diagnostic yield, (Fisher’s Exact p=0.16). As there were no non-diagnostic biopsies in the PBS group, the odds ratio was infinite and the upper confidence bound could not be estimated. Median dose of steroids was 213mg (prednisone equivalents; Q1 93mg, Q3 307mg). As all pts in the PBS group had diagnostic biopsies no analysis based on steroid dose could be conducted. All pts who received steroids had documented concern for vasogenic edema and steroids were not used for empiric treatment. Conclusions: In our cohort, pre-biopsy corticosteroid administration did not appear to affect diagnostic yield. There was no difference in the rate of diagnostic first biopsies between the PBS and steroid naive group. Among pts receiving steroids, all biopsies were diagnostic regardless of timing relative to biopsy or total steroid dose. Due to the small sample size and the universal diagnostic success, statistical comparisons were limited. These findings suggest that steroids may not compromise the diagnostic yield of PCNSL biopsies. Clinical characteristics and biopsy outcomes. Steroid NaiveN = 24 Steroids before Biopsy N = 35 p-value Age 69 (Q1 63; Q3 73) 66 (Q1 57; Q3 75) 0.3 Female 15 (63%) 19 (54%) 0.5 Normal LDH 16 (94%) 12 (67%) 0.088 ECOG 2-4 4 (16.6%) 9 (27.3%) 0.6 DLBCL 21 (88%) 32 (91%) 0.33 Total steroid dose 100-700mg (in Prednisone Equivalents) _ 23 (70%) Steroids within 24 hours of biopsy _ 14 (40%) Stereotactic needle biopsy 18 (75%) 17 (52%) 0.3 Diagnostic Biopsy 21 (91%) 33 (100%) 0.2
Interpretable machine learning to identify health system levers for survival outcomes of patients with prostate cancer.
1595 Background: Global disparities in prostate cancer outcomes are among the most pronounced across all cancer types. While incidence continues to rise globally, mortality reductions are more pronounced in countries with advanced healthcare systems. Understanding how health system factors relate to prostate cancer outcomes is critical for targeted policy interventions, particularly as the cancer burden is projected to rise substantially. We used explainable machine learning models to examine how these factors are associated with prostate cancer outcomes across countries. Methods: We compiled national mortality-to-incidence ratios (MIRs) for prostate cancer from GLOBOCAN 2022 and integrated them with system-level indicators from the WHO, the World Bank, UN agencies, and the Directory of Radiotherapy Centres (DIRAC). Variables included GDP per capita, the Universal Health Coverage (UHC) index, radiotherapy center density, physician and nursing workforce capacity, pathology services, and health expenditure composition. We implemented a CatBoost ensemble with repeated cross-validation and integrated SHAP (SHapley Additive exPlanations) for feature attribution to quantify country-level determinants of prostate cancer MIR while accounting for nonlinear, context-dependent relationships. Results: The model demonstrated strong predictive performance (R² = 0.796, RMSE = 0.078, correlation = 0.892). SHAP analysis identified radiotherapy center density, UHC index, and GDP per capita as the leading system drivers of MIR. Countries with robust radiotherapy capacity and comprehensive UHC consistently achieved lower MIR, whereas higher generic health spending alone showed a weaker correlation with outcomes. Yemen exhibited the highest MIR (0.720), driven by deficits in GDP, gender inequality, radiotherapy infrastructure, and UHC. The United States achieved the lowest MIR (0.107), driven by extensive radiotherapy density, high health expenditure, and robust coverage systems. Country-specific SHAP decompositions revealed heterogeneity: in higher-income settings, radiotherapy and health workforce predominantly lowered MIR, whereas in lower-SDI countries, lack of insurance and infrastructure remained major barriers. Conclusions: SHAP-empowered machine learning accurately predicts country-level prostate cancer MIR and provides actionable policy guidance. Investments in radiotherapy infrastructure and universal health coverage are likely to yield greater reductions in mortality than undifferentiated budget increases. This reproducible framework enables data-driven resource allocation and supports a precision-aligned approach to global cancer control, emphasizing equity, access, and the optimization of system-specific interventions.
Cross-stage validation of a multimodal machine learning model to predict pathological complete response to neoadjuvant chemotherapy or chemoimmunotherapy in resectable stage III non–small cell lung cancer.
8022 Background: Pathological complete response (pCR) after neoadjuvant chemoimmunotherapy is associated with improved outcomes in resectable non–small cell lung cancer (NSCLC), yet reliable tools to predict treatment response before surgery are lacking. Machine learning models have shown promise in advanced disease, but their ability to generalize across disease stages remains uncertain. We evaluated the performance of a machine learning model developed in stage IV NSCLC when applied to a cohort of patients with surgically resectable stage III disease treated with neoadjuvant chemotherapy or chemoimmunotherapy. Methods: The DEEP-Lung-IV study (NCT04994795) developed and validated machine learning models for personalized risk prediction based on multimodal data in patients with stage IV NSCLC treated with first-line pembrolizumab and/or chemotherapy. The models incorporated multimodal clinical routine data such as clinical, biological and CT-scan images. For the present study, the trained pre-treatment model was applied without retraining to patients enrolled in the NADIM trials (NCT03081689, NCT03081689) who received neoadjuvant chemotherapy alone (CTx), or in combination with nivolumab (Nivo+CTx), followed by surgery. Model performance was assessed using the area under the ROC curve (AUC) by considering only the last chest CT-scan image before surgery, or by combining it with other multimodal data. Results: A total of 103 patients with available clinical, biological, imaging data and who experienced surgery was considered for validation analysis (N = 88 patients with Nivo+CTx, N = 15 patients with CTx). When applied to the stage III NADIM cohort, the stage IV–derived model demonstrated strong predictive performance for pCR, with an AUC of 0.68 (95% CI, 0.57–0.78) in all patients using the CT-scan image only, rising to 0.76 (95% CI, 0.67–0.84) when additionaly leveraging on clinical and biological data. Performance was consistent across clinically relevant subgroups, especially in the patients treated with Nivo+CTx, with AUC estimates from 0.65 (95% CI, 0.54–0.76) using CT-scan image alone to 0.72 (95% CI, 0.61–0.82) when combined with the other multimodal data. The model was capable of handling missing predictor values, and preserved predictive value despite differences in disease stage and treatment intent. Conclusions: A machine learning model trained in advanced-stage NSCLC accurately predicted pathological response to neoadjuvant chemo- or chemoimmuno-therapy in a resectable stage III cohort, supporting the biological continuity of treatment response across disease stages. This cross-stage generalizability highlights the potential of machine learning–based tools to guide treatment personalization in earlier-stage NSCLC and warrants prospective validation.
Predicting treatment effect on distant recurrence free survival from functional tumor volume change during neoadjuvant therapy: A Bayesian hierarchical model of I-SPY 2 MRI and survival data.
618 Background: In neoadjuvant cancer trials, early endpoints that predict treatment effect on survival identify promising agents early and support accelerated regulatory approval. However, binary endpoints like pathologic complete response inadequately characterize the full distribution of residual disease in breast cancer, while promising continuous biomarkers like MRI derived functional tumor volume (FTV) are associated with survival outcomes but not widely collected. Using a Bayesian hierarchical model, long-term treatment effects on distant recurrence free survival (DRFS) can be predicted from continuous MRI-derived functional tumor volume (FTV) in the I-SPY 2 platform trial. Methods: I-SPY 2 treated 2117 patients from 2010-2022 (12 weeks of paclitaxel ± experimental agent followed by 4 cycles of doxorubicin + cyclophosphamide), and 1,859 underwent dynamic contrast-enhanced MRI at baseline and after 12 weeks of neoadjuvant therapy. MRI-derived functional tumor volume provided volumetric quantification of dynamic tissue enhancement. ΔFTV was defined as the ratio of 12-week to baseline FTV. A Bayesian joint hierarchical model (brms) fit treatment effects on ΔFTV and DRFS for each treatment regimen by HR/HER2 subtype, controlling for clinical nodal status, clinical T stage, grade, and calendar year. Arms with < 8 subjects are excluded. Performance was assessed using cross-validation, predicting DRFS treatment effects in one held out fold at a time from the learned ΔFTV-DRFS association in the remaining data, then comparing predicted to actual DRFS treatment effect. Sensitivity analyses on priors will be presented. Results: Across 1753 patients and 45 treatment–subtype combinations, the estimated treatment effects on ΔFTV and DRFS were highly correlated (posterior correlation -0.91; 95% CrI -1.00 to -0.23). Predicted DRFS treatment effect from ΔFTV demonstrated strong concordance with actual DRFS treatment effects (Pearson r = 0.94 in TNBC; 0.97 HER2+; 0.80 HR+HER2-). The top 5 treatment-subtype regimens ranked by predicted and actual DRFS were identical. 20 regimens predicted to have > 70% probability of DRFS benefit over subtype specific controls showed DRFS improvement, yielding 100% specificity and 69% sensitivity at this decision threshold. Conclusions: We demonstrate internally validated prediction of neoadjuvant treatment effect on DRFS from MRI-derived change in functional tumor volume in the I-SPY 2 trial of high-risk early breast cancer. This suggests continuous imaging measures capture a range of response to therapy while Bayesian approaches can be effective for predicting treatment effects. This encourages collecting MRI biomarkers in trials to facilitate validation as early endpoints supporting decisions in screening platform trials as well as regulatory accelerated approval.
Tremelimumab (T) + durvalumab (D) + chemotherapy (CT) vs pembrolizumab (P) + CT in 1L non-squamous (NSQ) metastatic NSCLC (mNSCLC) with <i>STK11</i> , <i>KEAP1</i> , and/or <i>KRAS</i> mutations (mut): Interim analysis (IA) of the phase 2b TRITON study.
8515 Background: Pts with STK11 , KEAP1 and/or KRAS -mutated mNSCLC may benefit from the addition of anti-CTLA-4 to anti-PD-(L)1-based chemo-immunotherapy. In the phase 3 POSEIDON study, 1L T+D+CT significantly improved OS vs CT in pts with mNSCLC. Exploratory analyses showed sustained OS improvement with T+D+CT vs CT in subgroups with STK11 , KEAP1 and/or KRAS mut; in each mut subgroup, magnitude of OS benefit with T+D+CT vs CT was numerically greater than with D+CT vs CT. The phase 2b, open-label, multicenter, US-based TRITON study is comparing 1L T+D+CT vs P+CT in pts with NSQ mNSCLC and STK11, KEAP1 and/or KRAS mut. Here we report results of a planned IA (data cutoff [DCO] 15 mo after 1st pt randomized) of objective response rate (ORR), duration of response (DoR) and safety. Methods: Pts with treatment [tx]-naïve, EGFR / ALK wild-type, NSQ mNSCLC and STK11 , KEAP1 and/or KRAS mut (ECOG PS 0/1) were randomized 1:1 to T+D+CT or P+CT. T+D+CT arm: T 75 mg + D 1500 mg + pemetrexed-platinum Q3W for 4 cycles, then maintenance D + pemetrexed Q4W until disease progression (PD); additional doses of T given at week 16 and, optionally, at mo 24. P+CT arm: P 200 mg + pemetrexed-platinum Q3W for 4 cycles, then maintenance P + pemetrexed Q3W until PD, for up to 24 mo. Randomization was stratified by mut type and tumor PD-L1 expression (≥1% vs <1%). The primary endpoint is PFS (RECIST v1.1; investigator-assessed) with planned sample size ~100 pts. Key secondary endpoints include OS, ORR, DoR and safety. Results: At DCO (12 Nov 2025), 41 pts were randomized to T+D+CT and 43 to P+CT. Overall, 27.4%, 21.4% and 78.6% of pts had STK11 , KEAP1 and KRAS mut (not mutually exclusive); 39.3% had PD-L1 <1%. In the T+D+CT vs P+CT arms, median (range) age was 69 (47–82) vs 69 (51–86) y, 48.8% vs 62.8% pts were male, 70.7% vs 72.1% were White and 14.6% vs 20.9% Black or African American, 78.0% vs 62.8% had ECOG PS 1. Median (range) safety follow-up for D/P was 5.6 (0.0–14.0)/5.1 (0.0–17.5) mo; median no. of D/P doses was 8/7. ORR (95% CI) was 39.0% (24.1–54.0) in the T+D+CT arm vs 34.9% (20.6–49.1) in the P+CT arm [unconfirmed ORR 48.8% (33.5–64.1) vs 41.9% (27.1–56.6)]. Median DoR (95% CI) was not reached (6.3–NR) vs 6.4 (4.2–NR) mo; 100% vs 58.3% pts remained in response at 6 mo. In KRAS mut-only pts (n=52; exploratory), ORR was 48.0% (12/25) with T+D+CT vs 33.3% (9/27) with P+CT. The sponsor remains blinded to PFS at this IA. With T+D+CT vs P+CT, 41.5% vs 41.9% of pts had Grade 3/4 AEs possibly related to tx (TRAEs); 2.4% vs 4.7% had TRAEs leading to tx discontinuation and 0% vs 2.3% had TRAEs leading to death. Conclusions: At IA, ORR and DoR results from the prospective TRITON study support a role for the addition of anti-CTLA-4 (T) to 1L anti-PD-L1 (D) + CT in pts with STK11 , KEAP1 and/or KRAS -mutated mNSCLC. Safety was similar in the two arms and consistent with known safety profiles. Clinical trial information: NCT06008093 .
IGNITE-Cerala: A phase II signal-seeking trial of ceralasertib targeting recurrent high-grade serous ovarian cancer with cyclin E1 overexpression with and without gene amplification.
5587 Background: Cyclin E1 ( CCNE1 ) gene amplification and protein over-expression is a marker of platinum resistance in high grade serous ovarian, fallopian tube or primary peritoneal cancer (HGSC). Preclinical studies in breast and HGSC models have identified cyclin E1 amplification or over-expression as a potential predictive biomarker for improved sensitivity to ATR inhibition. We aimed to assess the efficacy of ceralasertib, an ATR inhibitor, in HGSC with cyclin E1 over-expression. Methods: IGNITE is a multicentre, Phase 2 trial enrolling women with recurrent platinum resistant HGSC. Tumors were assessed for Cyclin E1 protein expression by IHC and CCNE1 copy number by FISH. Patients with evaluable disease by RECIST v1.1 or GCIG CA-125 criteria were included. Ceralasertib 160mg PO was given twice daily on days 1-14 of a 28-day cycle. The primary endpoint was investigator assessed overall response rate (ORR), defined as partial response (PR) or complete response (CR) at 16 weeks by RECIST v1.1 among patients with measurable disease, or by GCIG CA-125 criteria for patients with non-measurable disease. Here we present the 16-week response data for all patients treated with ceralasertib with a data cut-off of July 2025. Results: Between Feb-2024 and Apr-2025, 32 patients were accrued to IGNITE-Cerala. One patient was deemed ineligible after registration and was excluded. Median age was 64 years (range 40-76) and 74% had received ≥2 prior lines of chemotherapy. Median cyclin E1 IHC H-score was 190 (range 60 – 260). Twenty-seven patients (87%) had measurable disease by RECIST. Median number of cycles commenced was 3 (range 1-18). The ORR at 16 weeks was 10% (0 CR and 3 PR). The 6 month progression free survival estimate was 26% (range 12-42%). Treatment related adverse events (TRAE) were mostly grade 1-2 with the most common being gastrointestinal or hematologic. Six patients (19%) had Grade 3 TRAE, and one patient had Grade 4 TRAE. Six patients (19%) required a dose reduction, and no patients discontinued study drug due to toxicity. Conclusions: Ceralasertib was a well tolerated treatment, however responses did not appear to be enriched in a biomarker selected population and therefore future studies should consider rationale combinations with ceralasertib. Cyclin E1 over-expression and amplification remains an important biomarker in HGSC, with other strategies such as CDK2 or PK-MYT1 inhibitors under active investigation. Clinical trial information: ACTRN12619001185156. Response at 16 weeks Response evaluable patients (n=31) RECIST measurable patients (n=27) CR 0 (0%) 0 (0%) PR 3 (10%) 3 (11%) SD 7 (23%) 7 (26%) No CA-125 response and no PD 1 (3%) - PD 20 (65%) 17 (63%) ORR (CR/PR) 3 (10% [2, 26]) 3 (11% [2, 9])
ETHAN: A phase II study comparing different endocrine therapies for male breast cancer.
TPS656 Background: Male breast cancer is a rare disease, and most cases are hormone receptor-positive (HR+). Due to a lack of clinical trials, male breast cancer has historically been treated based on data extrapolated from women. However, there are substantial knowledge gaps in the comparative efficacy, safety, and patient-reported outcomes of endocrine therapies for men. While tamoxifen is the current standard of care, additional data are warranted for aromatase inhibitors (AI), gonadal suppression, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This is an open-label, multicenter, randomized, phase II trial designed to evaluate different endocrine therapies in men with HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. A total of 60 men will be enrolled across 9 sites within the Translational Breast Cancer Research Consortium (TBCRC). Key eligibility criteria include male sex and stage I, II, or III HR+/HER2- breast cancer before surgical resection of the primary tumor and axillary nodes. Key exclusion criteria include prior anti-cancer therapy within the past 12 months, and inflammatory breast cancer. The trial has two phases. The first phase is a window of opportunity in which newly diagnosed men are randomized 1:1:1 to either tamoxifen (Arm A), anastrozole (Arm B), or anastrozole plus degarelix (Arm C) given for 3 weeks. The primary endpoint for the window phase is Ki-67 reduction from the baseline diagnostic biopsy to the research biopsy at the end of the window phase. The second phase consists of neoadjuvant treatment, in which the tamoxifen group is randomized 1:1 to tamoxifen (Arm D) vs tamoxifen plus abemaciclib (Arm E), and the anastrozole alone (Arm B) and anastrozole plus degarelix (Arm C) groups are merged and then randomized 1:1 to anastrozole plus degarelix (Arm F) vs anastrozole plus degarelix plus abemaciclib (Arm G). The duration of the neoadjuvant phase is 4 months, and the primary endpoint of this phase is residual cancer burden (RCB) index at time of surgery. The trial is powered for the RCB endpoint in a 2 x 2 factorial design to detect a 0.6 unit decrease in RCB index with 80% power and alpha = 10%. For the Ki-67 endpoint, we assume an approximately 50% reduction in Arms A and B; Arm C will be of interest if it leads to ≥80% reduction in Ki-67. Secondary endpoints include: change in estradiol and testosterone levels from baseline, preoperative endocrine prognostic index (PEPI) score at surgery, adverse events, and patient-reported outcomes (including quality of life). Tumor tissue will be collected for correlative analyses. The study opened at Dana-Farber in October 2023, and is also open at Mayo Clinic, MD Anderson Cancer Center, Georgetown University, University of North Carolina, University of Pennsylvania, University of Pittsburgh, and Vanderbilt University. One more site will open in 2026. Clinical trial information: NCT05501704 .
Bone health and antiresorptive agent use in Asian American Pacific Islander (AAPI) women with breast cancer.
e12696 Background: AAPI women with breast cancer (BC) may be at increased risk for poor bone health due to lower bone mineral density (BMD) and prolonged antiestrogen therapy with a younger age at diagnosis. However, data on bone health screening, antiestrogen therapy-related bone loss, and antiresorptive agent (ARA) use in this population are limited. We compared bone health screening with dual energy x-ray absorptiometry (DXA), BMD after diagnosis, annual loss in BMD, and ARA use between AAPI and White women with BC. Methods: We conducted a multicenter retrospective study of AAPI and 1:1 random age-matched White women diagnosed with BC from 2020-2024 at 1 academic and 4 community sites. Primary outcomes included DXA screening rates within 1 year of diagnosis, BMD on initial DXA, and ARA use. Secondary outcomes included annual loss in total hip BMD. Multivariable logistic and linear regression models were used for statistical analysis. Results: 246 AAPI and 275 White women were analyzed. Mean (SD) age at diagnosis was 58 (13); 331 (65%) were postmenopausal, and almost all had stage 0-3 disease. AAPI had more stage 0 disease, lower body mass index (BMI), and were nonsmokers compared to White women (p < 0.05). Baseline DXA screening rates were similar in AAPI and White women (158 (64%) vs 185 (67%) respectively; adjusted OR 1.24, 95%CI 0.77-1.99). Mean baseline BMD at the spine, femoral neck, and total hip were significantly lower in AAPI women, and they had higher prevalence of osteoporosis 44 (28%) vs 31 (17%). The adjusted difference in spine BMD remained significant after controlling for menopausal status and BMI. Total hip BMD increased in White but remained unchanged in AAPI women, even when adjusted for menopausal status, BMI, aromatase inhibitor, and ARA use (Table 1). ARA use was low overall (23%) and did not differ significantly by race. Conclusions: Despite similar DXA screening rates, AAPI showed lower baseline BMD and more bone loss compared with White women with BC. These findings, together with low ARA use, suggest that current bone health management may be insufficient to mitigate antiestrogen therapy-related bone loss, particularly in AAPI women. Enhanced risk stratification, earlier intervention, and culturally-informed survivorship approaches, including optimization of bone-protective therapies, are needed to improve long-term skeletal outcomes in this AAPI population. Mean BMD & bone loss for AAPI & white women with BC. AAPIMean (SD) WhiteMean (SD) P-value Adjusted Mean Difference (95% CI)* Baseline Lumbar Spine BMD (g/cm 2 ) 0.92 (0.16) 1.00 (0.19) <0.0001 0.04 (0.01, 0.07) Baseline Femur BMD (g/cm 2 ) 0.69 (0.12) 0.73 (0.13) 0.017 0.01 (-0.01, 0.03) Baseline Hip BMD (g/cm 2 ) 0.86 (0.16) 0.90 (0.15) 0.049 0.00 (-0.03, 0.04) Annual Loss in Total Hip BMD (g/cm 2 /year) 0.00 (0.06) -0.14 (0.18) <0.0001 -0.13 (-0.18, -0.08) *Adjusted for menopausal status, BMI, aromatase inhibitor, and ARA.
Unintended access barriers: How upper payment limit implementation may risk patient access.
e23053 Background: Four states currently operate prescription drug affordability boards (PDABs) with purported authority to set Upper Payment Limits (UPLs; Colorado, Maryland, Minnesota, and Washington), while others are considering a range of state-level price setting mechanisms. These emerging policies, like the federal Inflation Reduction Act (IRA), introduce risks to patient access if, given existing incentives in plan coverage decisions, payers opt not to cover UPL drugs, place them on less favorable tiers, or apply utilization management (UM) to shift use to non-UPL drugs. To inform discussions around the potential risks of UPLs to patient access, we examined current coverage for policy-relevant oncology drugs in states with UPL authority. Methods: We analyzed pharmacy coverage, UM, and tiering, for the eight oral oncology drugs selected for or projected to be selected for the IRA’s Medicare Drug Price Negotiation Program. Using 2026 FingerTip Formulary data, beneficiary-weighted access was compared for included drugs between each PDAB state with UPL authority and aggregated access in the 46 other US states and District of Columbia (“non-UPL states”). We included health insurance exchange (HIX) and commercial plans, recognizing PDAB statutes vary in scope and may not apply to all ERISA-regulated self-funded plans. To conservatively represent access differences, differences of at least five percentage points were categorized as indicating “more” or “less” generous coverage, UM use, or preferred tiering. Results: Coverage for included drugs was generally similar in UPL and non-UPL states, apart from CO, where coverage was less generous for most drugs in HIX (n = 6/8) and commercial (n = 4/8) plans. Prior authorization (PA) barriers varied; compared to patients in non-UPL states, patients in CO and some in MD less often faced PA (CO commercial: n = 7/8 drugs; CO HIX: n = 6/8; MD HIX: n = 6/8), while commercially insured MN patients more often faced PA (n = 7/8). Step therapy was rare across drugs and states. Compared to patients in non-UPL states, those in three of four UPL states more often had access to included drugs on preferred tiers (HIX: MD, MN, WA; Commercial: CO, MD, MN). Conclusions: Patient access to oral oncology drugs in UPL states was often similar to – and sometimes better than – access in non-UPL states. These findings support concerns about future access waning through reduced coverage, adverse tiering, or increased UM, highlighting specific risks by state. For example, commercially- and HIX-insured patients in MD and MN more often have access to the included drugs on preferred tiers than those in non-UPL states; if UPLs were implemented, they may experience higher cost-sharing if plan sponsors placed the drugs on adverse tiers to steer patients towards non-UPL drugs. This research further informs discussion around meaningful PBM reforms that may improve patient access without UPL-associated risks.