Browse Articles

Corrigendum to “Impact of bridging the gap between Artificial Intelligence and nanomedicine in healthcare” [Next Nanotechnol. 8 (2025) 100203]

Neoadjuvant tyrosine kinase inhibitor therapy for unresectable locally advanced thyroid cancer: A systematic review and meta-analysis.

e18151 Background: Unresectable locally advanced thyroid cancers represent a rare clinical entity with a poor prognosis compared with early-stage disease. The absence of complete surgical resection is associated with markedly reduced five-year survival. In this context, neoadjuvant tyrosine kinase inhibitors (TKIs) have emerged as a strategy to induce tumor downstaging and facilitate surgical resection. In tumors with actionable genomic alterations, this approach may convert unresectable disease to resectable or allow less extensive surgery with reduced morbidity. Methods: We systematically searched PubMed, Embase, and Cochrane for studies (cohorts and clinical trials) evaluating neoadjuvant TKI therapy in adults with locally advanced, unresectable thyroid cancer, regardless of histology subtype. Studies evaluating adjuvant or purely palliative TKI therapy, other systemic treatments, combination regimens involving TKIs, and overlapping patient populations were excluded. All analyses were performed using R software (version 4.5.2). Pooled proportions were estimated using random-effects models, with heterogeneity assessed via I² statistics and Cochran’s Q test. Results: Among 1,053 screened records, six studies (five phase II clinical trials and one retrospective cohort) met the inclusion criteria, encompassing 144 patients, of whom 51.1% were male. All patients had locally advanced differentiated thyroid cancer and were treated with anlotinib, lenvatinib, apatinib, or selpercatinib. The reported median follow-up ranged from 6 to 34 months. The pooled R0/R1 resection rate was 81.8% (95% CI, 61.9–92.6; I² = 57.1%). The pooled objective response rate was 47% (95% CI, 38.7–55.5; I² = 26.1%). Partial responses were observed in 50.5% of patients (95% CI, 39.8–61.1; I² = 22.7%), while stable disease occurred in 46.4% (95% CI, 28.8–64.9; I² = 50.5%), resulting in a disease control rate of 95% (95% CI, 86.7–98.2; I² = 0%). Any-grade adverse events were reported in 89% of patients (95% CI, 60.9–97.7; I² = 50.1%) across three studies, with hypertension being the most frequently observed toxicity. Conclusions: In this rare disease setting, neoadjuvant TKI therapy demonstrated meaningful antitumor activity and enabled surgical resection in a substantial proportion of patients with initially unresectable thyroid cancer. However, evidence is limited by small cohorts, short follow-up, and high adverse event rates, highlighting the need for prospective studies to optimize patient selection.

Outcomes of neoadjuvant immunotherapy (NeoIO) in Merkel cell carcinoma.

9589 Background: Merkel cell carcinoma (MCC) is an aggressive malignancy with high rate of nodal and distant metastasis, leading to poor overall survival. For clinically detected regional lymph nodes, treatment typically involves node dissection with adjuvant radiotherapy. Evaluation of NeoIO in resectable MCC resulted in a pathological complete response (pCR) rate of 47%; pCR correlated with relapse-free survival (RFS). However, there is no standardized NeoIO regimen. We report our single institutional NeoIO experience in resectable MCC and correlate regimen with clinicopathological response. Methods: We retrospectively reviewed pts with resectable MCC who received NeoIO with intent to offer surgery (SX) or radiation (RT), from 2015 to present. Demographic and clinicopathological characteristics were evaluated. Overall Response Rate (ORR), pCR, and Relapse Free Survival (RFS) were computed. Overall survival (OS) was evaluated via a 90-day landmark Kaplan-Meier plot to assess if time to definitive regional treatment impacted OS. Results: We identified 25 patients; median age was 77 years old; 75% were male. Majority were clinical stage III (IIIa 20%; IIIb 68%); 12% were stage IIa. 32% had immunosuppression at the time of treatment. 36% had primary MCC on extremity, 36% on head and neck, 8% on trunk, and 20% were of unknown primary origin. 80% of patients received neoadjuvant Pembrolizumab, 16% Avelumab and 4% ipilimumab plus nivolumab. The median number of IO cycles was 3 (1-18); those who completed 1-2 cycles were more likely to receive SX/RT compared to those who received 3 or more cycles (p-value = 0.024). 64% of patients had an adverse effect during therapy; majority (87.5%) had G1/G2 events. 24 patients had post NeoIO imaging to which ORR was 75%. Post NeoIO, 15 underwent SX, 4 had definitive RT, 2 had progression of disease and received systemic therapy, 3 had comorbidities precluding treatment, and 1 was lost to follow up. The median time from beginning of NeoIO to SX or RT was 3 months (1-19mo). Of those who underwent SX, 40% had a complete pathologic response, 20% had a major pathologic response, 33% had a partial response, and 6% had non-response. With a median 23.4 months of follow-up, 8 of the 25 patients (32%) have experienced an event and the median EFS has not been reached. 7 of the 25 (28%) patients have died, 4 due to MCC; median overall survival not reached. Median follow up was 23.4 months. Time to event analysis indicated six patients who received NeoIO, followed with SX or RT within 90 days, had fewer deaths compared with those who received SX/RT after 90 days. Survival was approximately 3.5 years for those who did not receive SX/RT within 90 days and no deaths for those who received SX/RT within 90 days. Conclusions: NeoIO for MCC at our single institution achieved an ORR of 75% and a mPR/pCR of 60%. Earlier incorporation of regional therapy post NeoIO appears to improve outcomes, suggesting importance of multimodal management for resectable MCC.

The future of oncology research: Replacing case report forms with mCODE-aligned electronic health record data for clinical trial data curation (Alliance).

e13661 Background: The process of data abstraction and curation represents a significant proportion of clinical trial costs, requiring up to $30,000 per patient depending on the data complexity. Research variables such as stage, performance status (PS), and cancer disease status are typically present in the electronic health record (EHR) in free text but require abstraction for research use. Structuring these real-world data (RWD) in an exportable format utilizing minimum common oncology data elements (mCODE) could reduce the need for abstraction and the potential for erroneous transcription that has been shown to be 5.51-7.72% in a meta-analysis. We assessed the feasibility, availability, and accuracy of RWD for use across Alliance for Clinical Trials in Oncology sites by comparing RWD to matched electronic case report form data (CRF data) at 2 sites where EHR-integrated tools collect structured RWD for all solid tumor patients. Methods: Stage, PS, and cancer disease status (CDS) were extracted from the EHR as RWD and from eCRFs for 100 patients enrolled in National Clinical Trials Network trials across multiple disease sites from 2022 through 2025. Data from baseline and day 1 of cycles 1-4 were compared (500 encounter timepoints). Results: Stage, PS, and CDS were available from RWD more often than CRFs (85 vs 70 / 100 patients, 436 vs 416 / 500 encounters, and 345 vs 83 / 500 encounters respectively). When stage was present in both (n = 58), there were 5 mismatches (8.6%). PS had 22 mismatches (4%) and CDS had 45 mismatches (11.4%). After correcting for differences in CRF vs RWD definitions, CDS mismatches dropped to 1.2% (n = 4). Discordance between RWD and CRF data was related to differences in the timepoint of data collection (e.g., systemic staging scans completed after the initial consult), CRF data obtained from other EHR notes (e.g., oncology research nurse notes containing PS), inherent discordance between RWD and CRF data choices (e.g., responding vs complete or partial response), and failure to update EHR data capture tool fields. RWD were available 21 days (median) before CRF data. Conclusions: Our results suggest that RWD captured directly within clinical notes match CRF data, are more often present, and are available sooner. RWD could serve as a data source for trials, decreasing the need for manual curation and cost. Although some discordance exists, overall rates are low and close to the published error rate for abstraction.

Cardiovascular outcomes after bispecific T-cell-engager therapy in multiple myeloma: A propensity-matched real-world study.

e24007 Background: Bispecific T-cell engager (BiTE) therapies have emerged as highly effective immunotherapeutic agents for relapsed and refractory multiple myeloma by redirecting cytotoxic T-cell activity toward malignant plasma cells. However, immune activation associated with BiTE therapy may lead to systemic inflammation, cytokine release, and off-target effects, potentially increasing cardiovascular complications and healthcare utilization. Real-world evidence describing cardiovascular outcomes and longitudinal healthcare burden in this population remains limited. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, a federated electronic health record platform encompassing 70 healthcare organizations. Adult patients with multiple myeloma treated with BiTE agents (elranatamab, talquetamab, teclistamab, or linvoseltamab) were compared with BiTE-naïve multiple myeloma controls. The index date was defined as the first BiTE administration. Outcomes were assessed at 6 months and 1 year. Primary outcomes included all-cause mortality and emergency department (ED) visits or hospital admissions. Secondary outcomes included heart failure exacerbations, venous thromboembolism, major adverse cardiovascular events (MACE), and selected cardiovascular endpoints. Propensity score matching (1:1) was performed using demographic, clinical, procedural, medication, and laboratory variables. Time-to-event analyses utilized Kaplan–Meier methods and Cox proportional hazards models. Results: After matching, 843 BiTE-treated patients were compared with 843 non-BiTE controls with excellent covariate balance. At 6 months, mortality was numerically higher in the BiTE group but not statistically significant (15.8% vs 13.9%; hazard ratio [HR] 1.22; p=0.286). BiTE therapy was associated with significantly increased ED visits or hospital admissions (58.1% vs 37.7%; HR 2.00; p<0.001) and higher heart failure exacerbations (17.9% vs 11.9%; HR 1.63; p<0.001). No significant differences were observed in venous thromboembolism or MACE. At 1 year, excess ED visits or hospital admissions (63.3% vs 45.2%; HR 1.98; p<0.001) and heart failure exacerbations (19.6% vs 14.0%; HR 1.58; p<0.001) persisted. Mortality showed a nonsignificant trend toward higher risk in the BiTE group (20.3% vs 19.0%; HR 1.24; p=0.054). Conclusions: In this large real-world cohort, BiTE therapy in multiple myeloma was associated with increased healthcare utilization and heart failure exacerbations without a statistically significant increase in mortality or thrombotic events. These findings emphasize the need for cardiovascular risk surveillance and multidisciplinary management in patients receiving BiTE therapies.

Efficacy and safety of lunbotinib (A400/EP0031), a next-generation selective RET inhibitor (SRI), from a pivotal phase II study in patients with advanced <i>RET</i> fusion–positive non–small cell lung cancer (NSCLC).

8505 Background: RET-fusion positive NSCLC accounts for 1-2% of all lung cancers. Lunbotinib is a next gen brain-penetrant SRI with high potency against RET fusion and mutant proteins ( Zhou et al., 2023; Alonso et al., 2025 ). We report findings from a pivotal phase Ⅱ study in advanced RET-fusion positive NSCLC in China (NCT05265091). An ongoing study is assessing lunbotinib alone or in combination with chemotherapy in Western patients (pts) (NCT05443126). Methods: The phase Ⅱ part enrolled two single-arm cohorts: cohort 1 included pts with prior platinum-based chemotherapy and immunotherapy (pre-treated), and cohort 2 included treatment-naïve pts. All pts received oral lunbotinib 90 mg once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was ORR assessed by an independent review committee (IRC) per RECIST v1.1. Results: As of Oct 29, 2025, 71 pre-treated pts and 92 treatment-naïve pts were enrolled, with median follow-up of 22.6 and 20.7 mos, respectively. Among pre-treated and treatment-naïve pts in full analysis set (FAS), ECOG PS 1 rates were 90% and 80.2%, and metastases involving ≥3 organ sites were observed in 75.7% and 57.1%. IRC-assessed confirmed ORR was 87.1% (95% CI: 77.0-93.9) in pre-treated pts and 81.3% (95% CI: 71.8-88.7) in treatment-naïve pts. mPFS was 27.5 mos and NR, respectively. Among pts with baseline CNS metastases (23 pre-treated, 16 treatment-naïve), ORR was 82.6% and 75.0%, respectively, and 6 pts in each cohort had complete intracranial response. Full efficacy data are in Table. Treatment-related AEs (TRAEs) occurred in 98.8% of pts, the most common were AST (72.4%), ALT (68.1%), anemia (63.2%), urinary retention (45.4%), dry eye (43.6%), and increased blood creatinine (42.9%). Grade ≥ 3 TRAEs observed in 40.5%. Two pts (1.2%) discontinued due to TRAEs. No fatal TRAEs occurred. Conclusions: Lunbotinib demonstrated robust efficacy in pts with advanced RET-fusion positive NSCLC, with high ORR and prolonged PFS in both pre-treated and treatment-naïve populations, and notable intracranial activity. Safety profile was manageable, with no new signals identified. These data support the potential of lunbotinib as a valuable therapeutic option for this population. Clinical trial information: NCT05265091 . Pre-treated pts (Cohort 1) N=71 Treatment-naïve pts (Cohort 2) N=92 Confirmed ORR a /DCR a , % (95% CI) 87.1 (77.0, 93.9)/ 91.4 (82.3, 96.8) 81.3 (71.8, 88.7)/ 92.3 (84.8, 96.9) mDoR a (95% CI), mo 25.7 (14.8, NE) NR (NE, NE) 24-mo DoR rate, % (95% CI) 55.4 (41.1, 67.5) NE mPFS (95% CI), mo 27.5 (16.1, NE) NR (19.4, NE) 24-mo PFS rate, % (95% CI) 52.1 (39.3, 63.5) 59.9 (47.8, 70.0) mOS (95% CI), mo NR (26.1, NE) NR (NE, NE) 24-mo OS rate, % (95% CI) 65.7 (51.5, 76.6) 74.1 (62.1, 82.8) Baseline CNS metastases, n 23 16 ORR, % (95% CI) 82.6 (61.2, 95.0) 75.0 (47.6, 92.7) a In FAS; N was 70 and 91.

Multi-disciplinary discharge coordination team to overcome discharge barriers and address the risk of delayed discharges.

e23318 Background: Efficient discharge planning is essential in healthcare, especially for oncology patients with complex needs. Delayed discharges lead to longer hospital stays, higher costs, and fewer available beds. This study explores the use of a Multi-Disciplinary Discharge Coordination Team (MDDCT) to overcome these challenges and reduce the risk of delays. Methods: A quantitative study was conducted involving the analysis of discharge times, follow-up appointments, length of stay, bed turnover rate, and patient satisfaction. The MDDCT, comprising physicians, nurses, pharmacists, social workers, and case managers, was tasked with remapping the discharge process. This included identifying and eliminating bottlenecks using lean methodology, performing daily rounds, and employing an electronic tracking tool to monitor patient progress and discharge readiness. Data were collected from electronic health records and medical records, and statistical analysis was conducted using STATA 18 software. Results: The implementation of the MDDCT resulted in significant improvements in discharge planning. The average length of stay for patients decreased from 6.2 days in 2020 to 4.3 days in 2023. Bed turnover rates increased 4.79 in Q1 2021 to 5.5 Q12024, indicating more efficient use of hospital beds. Additionally, the percentage of missed follow-up appointments post-intervention dropped to 0%, demonstrating improved patient adherence to post-discharge care plans. Turnaround time for discharge medication preparation was reduced from 185 minutes in September 2021 to 118 minutes in March 2023, thanks to the establishment of a dedicated satellite pharmacy and enhanced prescription interfaces. The findings corroborate existing literature on the benefits of multi-disciplinary teams in healthcare. The MDDCT's holistic approach to discharge planning ensured comprehensive post-discharge care, reducing delays and improving patient outcomes. The study's implications suggest that hospitals should integrate MDDCTs into their discharge protocols to enhance efficiency and patient satisfaction. However, limitations such as the reliance on self-reported data and focus on a single hospital highlight the need for broader multi-site studies. Conclusions: Implementing MDDCT is crucial for overcoming discharge barriers and reducing delayed discharges. This approach ensures a seamless transition from hospital to home, optimizing resource use and enhancing patient care. Continuous improvements, including lean methodology and refined documentation practices, are vital for efficient and effective discharge planning.

Identifying gastric cancer risk before cancer suspicion: <i>Helicobacter pylori</i> prevalence and virulence heterogeneity in a multicenter endoscopy cohort.

e22534 Background: Gastric cancer remains a leading cause of cancer mortality worldwide. Helicobacter pylori is a WHO class I carcinogen, yet its detection and characterization in real-world, non-oncologic endoscopy populations remain limited. Identifying modifiable gastric cancer risk before cancer suspicion represents a critical prevention opportunity. Methods: This was a multicenter, cross-sectional study of patients undergoing upper endoscopy for non-oncologic indications at a tertiary center in Mexico. Clinical, endoscopic, histopathologic and lifestyle variables were collected. Gastric biopsies were evaluated by H&amp;E and molecular assays for H. pylori , five virulence-associated genes were identified. Prevalence was estimated with exact 95% Confidence Intervals (CI). Exploratory group comparisons used contingency tables with chi 2 of Fisher exact tests, as appropriate, bilateral p-values were interpreted descriptively. Results: Among 92 biopsies tested molecularly, H. pylori was detected in 28.3% (n = 26, CI 19.4–38.6). In the paired analytic cohort with clinical and questionnaire data (n = 89), H. pylori was identified histologically in 11 samples and differed significantly across gastritis severity categories (p = 0.007), with higher inflammatory activity among positive samples. Premalignant lesions were present in 10% of patients. Molecular profiling revealed substantial virulence heterogeneity, vacA was detected in 85% (n = 22) of H. pylori- positive biopsies, with a wide quantitative range (max. &gt; 17,000 copies), cagA was not detected, while other virulence associated genes showed variable presence. Exploratory analyses suggested associations between H. pylori infection and select socioeconomic and lifestyle factors, including consuming non-purified water. Despite evidence of carcinogenic infection, referred prior eradication therapy was rare. Conclusions: In real-world endoscopy cohort without cancer suspicion, H. pylori infection and inflammation-associated risk states are common and frequently untreated. Results of the characterization and count of virulence-associated genes, suggests risk is not necessarily binary (infected vs not), rather graded, biologically plausible, and measurable at the point of routine care. Treating risk as graded supports pragmatic prevention strategies and endoscopy-based pathways to identify and treat high-risk states.

Patent claim landscape of FDA Orange Book–listed oral oncology drugs: A systematic analysis of standard practice claims.

e23042 Background: Patents listed in the FDA Orange Book influence the timing of generic drug entry. While intended to protect innovation, Orange Book patents increasingly include secondary claims related to dosing, administration, and treatment use that may overlap with routine oncology practice. We systematically evaluated the scope and clinical relevance of Orange Book patent claims for oral small-molecule oncology drugs using a clinical “person of ordinary skill in the art” (POSITA) framework. Methods: We conducted a cross-sectional analysis of all oral small-molecule oncology drugs listed in the FDA Orange Book as of December 2024. Patents were retrieved from USPTO and Google Patents databases. Claims were manually extracted and categorized using a 16-category framework reflecting common oncology decision points and common claim descriptions. Claim sets (independent claim plus dependents) were the unit of analysis. Patent portfolio characteristics, claim co-occurrence, and references to human clinical evidence were analyzed descriptively. Results: Seventy-eight drugs were associated with 543 Orange Book patents comprising 10,311 claims and 1,514 claim sets. Clinically oriented claim categories were common, including therapeutic indication (39%), route of administration (32%), listed dose (28%), and implicit dosing or dose modification (25%). Overall, 58% of claim sets contained at least one element categorized as routine clinical practice, compared with 21% containing claims considered potentially less likely routine (e.g., biomarker-based selection). Co-occurrence analysis showed frequent bundling of standard-practice elements, including dose with formulation (Jaccard index 0.51) and timing with treatment line (0.40). Only 23% of patents referenced any human clinical data; among these, 68% cited Phase I or observational evidence only, and 16% referenced Phase III trials. Drugs with larger and more diverse patent portfolios had longer effective protection durations (Spearman ρ ≈ 0.42, p &lt; 0.01). Conclusions: Orange Book patents for oral oncology drugs frequently include claims overlapping with routine clinical practice, often supported by limited clinical evidence. Bundling of standard-practice claims is common and associated with prolonged protection timelines, raising questions about the alignment between patent scope, clinical innovation, and generic access as it relates to Orange Book listings.

Real-world treatment patterns and outcomes with olutasidenib after venetoclax in <i>IDH1</i> -mutated AML using EHR data.

e18514 Background: Venetoclax (VEN) plus a hypomethylating agent is standard front-line therapy for patients with AML ineligible for intensive chemotherapy; however, most patients will ultimately relapse. Olutasidenib (OLU), a selective oral inhibitor of mutated IDH1 (m IDH1 ), is approved for relapsed/refractory (R/R) m IDH1 AML. In the pivotal Phase 2 trial, OLU achieved CR/CRh in 35% of patients (median CR/CRh duration 25.3 months) with acceptable tolerability. Real-world data on OLU utilization and outcomes in practice are limited. Methods: This retrospective cohort study used Loopback Analytics’ EHR database (Oct 2016 to Oct 2025), incorporating structured and unstructured data. Eligible patients were ≥18 years old with confirmed m IDH1 R/R AML, a prior VEN regimen, ≥25 days of OLU, and a documented response assessment. Treatment response was categorized as CR, CRh, CRi, or MLFS. Baseline demographics, treatment sequences, and clinical outcomes were summarized using descriptive statistics. Overall Survival (OS) and duration of response (DoR) were estimated using Kaplan-Meier methods. Results: Twenty-four OLU-treated patients met the inclusion criteria. Median age at OLU initiation was 67 years, and 63% of patients were male. Four patients (17%) received a hematopoietic stem cell transplant (HSCT) prior to OLU. Most patients (75%) presented with at least one co-occurring mutation; most commonly FLT3 (33%), NPM1 (29%), and RUNX1 (21%). Median duration of OLU treatment was 4.0 months (IQR 1.7-6.5 months) and OLU was administered as monotherapy in 54% of patients. Over half (58%) of patients received VEN as front-line therapy, primarily with HMA. OLU was second-line therapy in 42% of cases and immediately followed VEN in 83% of cases. The median number of prior lines was 2. The most common reason for OLU discontinuation was disease progression. The ORR was 58% (4 CR, 5 CRi, 1 CRh, and 4 MLFS) with a CRc rate of 42%. Among patients who achieved any response, 10 (71%) received OLU as the next line following VEN. Among patients with front-line VEN and second-line OLU, the ORR was 60% and the CRc rate was 50%. Median duration of CRc was 11.9 months (n=8 with evaluable DoR) with 2 having ongoing response at data cutoff and 2 having ongoing response at HSCT. In the overall population, four patients went to HSCT. Median OS from OLU initiation was 11.6 months, with the proportion of patients surviving 6, 9, and 12 months estimated to be 80%, 72%, and 43%, respectively. Conclusions: This study offers real-world insights into OLU treatment and outcomes in post-VEN m IDH1 R/R AML patients. OLU was used as monotherapy in half of patients, often directly following VEN. In this cohort, 58% of patients responded with 42% achieving CRc, consistent with efficacy observed in the subset of post-VEN patients from the pivotal Phase 2 trial. These findings support OLU as a viable post-VEN option, although additional data are needed.

Patient-reported outcomes from the adjuvant ado-trastuzumab emtansine (T-DM1) for older patients with HER2+ breast cancer (ATOP) trial.

635 Background: Prospective data on efficacy, quality of life, and treatment-related toxicities in older adults with breast cancer are limited. The ATOP trial (NCT03587740) evaluated T-DM1 in older adults and demonstrated favorable 5-year invasive disease-free survival. Here, we report patient-reported adverse events (AEs) and health-related quality of life (HRQOL) findings from ATOP. Methods: ATOP was a single-arm, phase II, multicenter study of adjuvant T-DM1 for those aged 60 with stage I-III HER2+ breast cancer. Protocol therapy included postoperative administration of T-DM1 (3.6 mg/kg) every 21 days for one year (17 cycles). PRO-CTCAE (assessing specific symptoms) and EQ-5D (a measure of HRQOL) surveys were administered electronically or on paper at baseline (pre-treatment), on Day 1 of each treatment cycle, and at a single 6–12-month post-treatment time point. Participants who responded to the baseline and at least one follow-up survey were included in the PRO analysis. EQ-5D changes from baseline were assessed using general linear mixed models. Summary statistics were used to assess PRO-CTCAE scores to evaluate which symptoms developed between baseline and 1 subsequent survey(s) and their severity. Results: Among the 111 patients enrolled on ATOP (median age=71, range 60-88 years), 98 responded to the baseline survey and 1 subsequent survey(s). 1435 surveys were returned that included at least one PRO-CTCAE response, and 1661 surveys were returned that included EQ-5D. The Table displays the % of participants who reported PRO-CTCAE symptoms that worsened from baseline to any severity level (scores &gt;0) or to a severe level (scores ≥3). More than 60% of survey respondents reported new or increased dry mouth, fatigue, muscle aches, decreased appetite, nausea, pain, and/or numbness/tingling at some point during or after treatment, but these were usually not severe. EQ-5D scores did not change significantly from baseline at any time point. Conclusions: In this adjuvant trial for patients aged &gt;60, participation rates for PRO data collection were high. Reassuringly, global HRQOL was not impacted by T-DM1, and though frequently reported, the vast majority of patient-reported symptoms were mild. Future analyses of this trial will focus on duration and predictors (clinical and biomarker-based) of severe AEs, agreement between patient-reported and clinician-reported AEs, and whether sharing PRO reports with clinicians impacted clinician-reported AE grades. Clinical trial information: NCT03587740 . Most common new or worsening symptoms reported via PRO-CTCAE in ATOP (n=95). Symptom % with score &gt;0 n (%) with score 3+ Dry mouth 79% 26% Fatigue 71% 29% Muscle aches 69% 20% Decreased appetite 69% 12% Nausea 67% 6% Pain 66% 21% Numbness/tingling 65% 9% Blurry vision 60% 4% Mouth or throat sores 60% 5%

Effect of ripretinib on the pharmacokinetics (PK) of midazolam (MDZ), a sensitive CYP3A probe substrate, in adult patients (pts) with advanced gastrointestinal stromal tumor (GIST).

e23509 Background: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) indicated for the treatment of adult pts with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and/or DP-5439 (active metabolite) showed weak time-dependent inhibition and weak induction of CYP3A in vitro. MDZ is metabolized by CYP3A in the gut and liver to 1′-hydroxy-midazolam (1′-OH MDZ), making it an ideal probe substrate for CYP3A activity. This open-label study evaluated the effect of ripretinib on the PK of MDZ in pts with advanced GIST who progressed on or had intolerance to 3 or more prior TKI therapies. Methods: A single oral 2-mg MDZ dose was administered on cycle 1 day 1 (C1D1) to 18 pts in a fasted state. Ripretinib 150 mg once daily was administered beginning on C1D3. On C1D12, a single 2-mg MDZ dose was coadministered with ripretinib. Ripretinib was continued until disease progression, unacceptable toxicity, or withdrawal of consent. PK samples were collected predose through 48 hours postdose on C1D1 and C1D12 and analyzed for MDZ and 1′-OH MDZ. PK parameters were calculated using noncompartmental analysis; ln-transformed PK parameters for MDZ and 1′-OH MDZ were compared using ANOVA with treatment (with ripretinib vs alone) as a fixed effect and pt as a random effect. Geometric mean ratios and 90% confidence intervals (CIs) for maximum concentration (C max ), area under the curve from time 0 to last quantifiable concentration (AUC 0-t ), and AUC extrapolated to infinity (AUC 0-∞ ) were computed. Patient safety was monitored. Results: Of 18 pts, 16 (89%) were PK evaluable. MDZ and 1’-OH MDZ C max , AUC 0-t , and AUC 0-∞ were similar with ripretinib vs alone; 90% CIs were within bioequivalence limits. Time to reach C max , half-life, and metabolite ratios were generally unchanged. All 18 pts (100%) had at least 1 treatment-emergent adverse event (TEAE); 3 pts (17%) had grade 3/4 TEAEs, of which 1 pt (6%) had a fatal outcome (disease progression). All the AEs were unrelated to study treatment. Conclusions: Ripretinib did not alter the PK of MDZ. Therefore, ripretinib is not a clinically relevant CYP3A modulator. Ripretinib exhibited a manageable safety profile consistent with its established use in advanced GIST. Clinical trial information: 2022-501477-40-00. Plasma PK parameters of MDZ and 1’-OH MDZ. Parameter MDZ Reference n = 16 MDZ + ripretinib Test n = 16 Geometric mean ratios (90% CI) MDZ C max , ng/mL 15.5 (32.4) 17.7 (32.7) 1.14 (1.04, 1.25) AUC 0–t , h·ng/mL 39.8 (65.9) 43.9 (39.6) 1.10 (0.969, 1.25) AUC 0–∞ , h·ng/mL 43.6 (62.8) 46.9 (38.0) 1.08 (0.950, 1.22) 1’-OH MDZ C max , ng/mL 4.87 (47.1) 5.34 (41.5) 1.10 (1.00, 1.20) AUC 0–t , h·ng/mL 11.0 (42.7) 11.4 (37.3) 1.03 (0.909, 1.17) AUC 0–∞ , h·ng/mL 12.1 (47.5) a 12.6 (36.5) b 1.07 (0.918, 1.24) Data presented as geometric mean (% geometric coefficient of variation) unless otherwise noted. a n = 13. b n = 15.

Real-world treatment patterns and overall survival (OS) in patients (pts) with HER2-positive (HER2+) advanced or metastatic gastroesophageal adenocarcinomas (mGEA) in the US.

4053 Background: The first-line (1L) standard of care for pts with HER2+ mGEA is HER2-targeted therapy (HER2 Tx) plus platinum-based chemotherapy (CT). Recent immunotherapy (IO) addition to this regimen prolonged OS of pts with HER2+ programmed death-ligand 1 (PD-L1)-positive (PD-L1+) mGEA. Here, we describe real-world treatment patterns and OS in pts with HER2+ mGEA in the US since the FDA approval of 1L IO. Methods: Adults with HER2+ mGEA who initiated 1L systemic therapy between May 2021 and 2025 and had ≥6 mo of follow-up (or died within 6 mo) after 1L initiation, were identified from the Flatiron Health Electronic Health Records database. OS from 1L initiation was evaluated with the Kaplan-Meier method in the overall HER2+ cohort and in a subset of pts with PD-L1+ disease. Outcomes were also reported with HER2 Tx + CT ± IO use. Results: Of 2237 pts with known HER2 status prior to 1L therapy, 21% were HER2+, defined as immunohistochemistry (IHC) 3+, IHC 2+/ ERBB2 -amplified, or per physician’s note. Mean (SD) age was 66.1 (11.7), 20% of pts were female, and 66% had an Eastern Cooperative Oncology Group performance status ≤1. Of 292 pts with HER2+ mGEA and known PD-L1 status prior to 1L, 81% were PD-L1+ (combined positive score ≥1 or per physician’s note). Of the 467 pts with HER2+ mGEA who received 1L therapy, 60% had HER2 Tx, 28% had CT alone, and 10% received IO-based regimens without HER2 Tx. Of the 281 pts on 1L HER2 Tx, 58% had HER2 Tx + IO + CT and 37% had HER2 Tx + CT. Overall, 228/467 (49%) pts treated in the 1L went on to receive second-line (2L) therapy. In the 2L setting, 70% of pts received HER2 Tx, including 38% pts who only received CT or IO-based regimens without HER2 Tx in 1L treatment. A total of 42% of pts on 2L therapy received 1L and 2L HER2 Tx. Among the 467 pts with HER2+ mGEA, median OS (mOS) from 1L initiation was 17.4 mo. In the PD-L1+ subgroup, mOS was 19.0 mo in pts on HER2 Tx + IO + CT, and 17.2 mo in pts on HER2 Tx + CT without IO (Table). Across treatment groups, mOS remained &lt;2 years, and the 24-mo OS rate was &lt;40%. Conclusions: Despite the availability of HER2 Tx, a significant unmet need remains, as 40% of pts with HER2+ mGEA did not receive this option in 1L regimens. OS was numerically longer with HER2 Tx + IO + CT vs without IO in the HER2+/PD-L1+ mGEA subgroup. These data underscore the need to improve OS and the opportunity to enhance biomarker-guided management of HER2+ mGEA. OS analysis. HER2+ HER2+/PD-L1+ Subgroup HER2+ (Overall) 1L HER2 Tx + IO + CT 1L HER2 Tx + CT PD-L1+ (all) 1L HER2 Tx + IO + CT 1L HER2 Tx + CT (n = 467, 100%) (n = 164, 35%) (n = 103, 22%) (n = 237, 100%) (n = 95, 40%) (n = 40, 17%) Median OS, mo 17.4 19.3 17.2 17.2 19.0 17.2 (95% CI) (15.7, 20.5) (15.7, 22.3) (13.5, 21.3) (15.0, 20.9) (15.6, 24.6) (12.6, 24.4) OS Rate, (%)  6-mo 83.0 85.5 79.8 82.3 87.2 77.5  12-mo 65.5 67.6 66.4 64.1 67.9 66.2  18-mo 48.9 52.4 46.3 47.2 53.0 41.7  24-mo 34.7 37.2 26.3 36.0 39.5 30.6

Pirtobrutinib in treatment-naïve patients with CLL/SLL: Pooled results from BRUIN CLL-313 and BRUIN CLL-314.

7044 Background: Pirtobrutinib, a highly selective, non-covalent Bruton tyrosine kinase inhibitor (BTKi), is approved globally for patients (pts) with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTKi. BRUIN CLL-313 and BRUIN CLL-314 are open-label, randomized phase 3 studies evaluating pirtobrutinib for therapy of pts with CLL/SLL, including in the treatment-naïve (TN) setting [versus bendamustine plus rituximab (BendaR; CLL-313, NCT05023980) and versus ibrutinib (CLL-314, NCT05254743)]. Methods: Pooled data from TN CLL pts randomized to receive pirtobrutinib from CLL-313 and CLL-314 were used to assess efficacy [overall response rate (ORR), progression-free survival (PFS) and overall survival (OS)] and safety. PFS and OS estimates were calculated by the Kaplan-Meier method. All pts (253) randomized within each study to receive pirtobrutinib are included in efficacy analyses and all pts (252) who received pirtobrutinib treatment are included in safety analyses. Results: A total of 253 TN pts, median age of 66 yrs, were assigned to receive pirtobrutinib (CLL-313 n=141; CLL-314 n=112); all but one received treatment. Among pts with evaluable samples 134/233 (58%) had unmutated IGHV, 14/253 (6%) had del(17p) and 21/220 (10%) had mutated TP53. Efficacy was consistent between the two studies (Table). Overall, ORR was 93.3%. Median PFS was not reached; the 24-month PFS rate was 93.2% (95%CI, 89.1-95.8). Median OS was also not reached; the 24-month OS rate was 97.5% (95%CI, 94.6-98.9). Median duration of therapy was 29.1 months. Treatment discontinuation due to TEAEs occurred in 4.8% of pts with 1.6% treatment related. Any-grade infection occurred in 59.9% of pts; neutropenia in 18.3% and grade ≥3 bleeding in 2.4%. Any-grade hypertension occurred in 10.7% of pts and atrial fibrillation/flutter was reported in 2.8%. Conclusions: In 253 TN pts with CLL randomized on two phase 3 studies, pirtobrutinib showed a high ORR and favorable 24-month PFS and OS rates. The safety profile was consistent with prior studies using pirtobrutinib in more heavily treated pts, with low rates of atrial fibrillation/flutter, hypertension and TEAE-related discontinuations. These findings reinforce the potential of pirtobrutinib as a meaningful and clinically relevant treatment option for pts with TN disease. Clinical trial information: NCT05023980 and NCT05254743 . Efficacy of pirtobrutinib in TN patients with CLL/SLL. Parameter CLL-313N = 141 CLL-314N = 112 Pooled TN ptsN=253 ORR ORR, % (95% CI) 94.3 (89.1, 97.5) 92.0 (85.3, 96.3) 93.3 (89.5, 96.0) PFS 24-month PFS rates, % (95% CI) 92.7 (86.8, 96.0) 94.3 (87.8, 97.4) 93.2 (89.1-95.8) Median FU, months 28.1 22.4 27.7 OS 24-month OS rates, % (95% CI) 97.8 (93.3, 99.3) 97.2 (91.5, 99.1) 97.5 (94.6-98.9) Median FU, months 32.7 26.7 29.5 ORR includes a best response of partial response or better.

The efficacy and safety of add-on ruxolitinib for patients with severe checkpoint inhibitor pneumonitis management with corticosteroids: A multicenter, open-label, randomised phase 2 trial.

12016 Background: Checkpoint inhibitor pneumonitis (CIP) stands out as a remarkable complication during ICIs therapy. Severe CIP represents a potentially life-threaten immune-related adverse event (irAE) with limited evidence from clinical trials that guides therapeutic interventions. Ruxolitinib, a selective JAK1/2 inhibitor, effectively attenuates cytokine-release syndrome and show significant anti-fibrotic in mouse lung with BLM model. We conducted a multicenter, investigator-initiated, open-label, phase 2 randomized controlled trial to evaluate the efficacy and safety of add-on ruxolitinib for patients with severe CIP management with corticosteroids. Methods: Patients with malignant who were suffered from CTCAE grade (G) 3 or G4 CIP after ICIs therapy were screened. Enrolled CIP patients were randomly assigned 1:1 to control group (only glucocorticoids) or ruxolitinib group (glucocorticoids plus ruxolitinib). Initiated dosage of glucocorticoids was no less than prednisone 1 mg/kg/day (or same steroid equivalent dose) with subsequent tapering off. In ruxolitinib group, enrolled patients were add-on ruxolitinib (5 mg twice daily for 2 weeks, followed with 5 mg daily for 2 weeks). The primary end point was the proportion of patients with a prednisone daily dosage of no more than 10mg and improvement to G1 CIP at week 8. Continuous variables were analyzed using a mixed-effects model for repeated measures with treatment group, study visit and treatment-by-visit interaction. Results: From April 2023 to November 2025, a total of 60 eligible patients were recruited and randomly assigned to control group and ruxolitinib group. There were 52 cases of G3 CIP and 8 cases of G4 CIP. There were more patients in the ruxolitinib group improved to G1 CIP and received ≤prednisone 10mg daily at 8 th week than in the controlled group (20cases/66.7% vs 11cases/36.7%, p = 0.0379 ). This effect was more significant in the 2 nd and 4 th week. Two patients in ruxolitinib group and 4 patients in the control group died within eight weeks. The repeated measures analysis using a generalized linear mixed model demonstrated a significant overall treatment effect, ie. add-on ruxolitinib was associated with significantly higher odds of clinical improvement (adjusted OR = 5.12, 95% CI 1.06 - 24.64; p = 0.04). A total of 13 G3 or higher treatment-related AEs (TRAEs) occurred (7 cases in control group and 6 cases in ruxolitinib group), including 9 cases of infectious diseases. Conclusions: Add-on ruxolitinib for malignant patients with severe CIP management with glucocorticoids show with higher resolution rates and earlier response trends than only glucocorticoids treatment. And there were no different adverse events between them. Add-on ruxolitinib with glucocorticoids might be a promising proposed treatment for patients with severe CIP. Clinical trial information: NCT05899725 .

Association of proton pump inhibitor use with cancer-specific mortality in a nationally representative U.S. cohort (NHANES, 1999–2018).

10625 Background: Proton pump inhibitors (PPIs) are widely used and often continued beyond recommended durations. Evidence linking chronic PPI use to adverse cancer outcomes and mortality is mixed. Potential mechanisms include hypergastrinemia, altered gastric mucosa, and microbiome changes that may influence tumor behavior and treatment response. We assessed the association between baseline PPI use and cancer-specific mortality in a nationally representative U.S. cohort. Methods: Ten NHANES cycles (1999–2018) linked to the NHANES Linked Mortality Files (1999–2018) were pooled. Adults ≥18 years who were mortality-eligible and had examination follow-up time (PERMTH_EXM) were included. A formal written protocol was not developed; the analysis plan (study objective, exposure, endpoint, covariates, and primary models) was prespecified through discussion with the study team prior to final analyses. Baseline PPI exposure was defined from the 30-day prescription medication inventory (container-verified when available). A curated text algorithm identified PPIs using generic/brand/OTC names and fixed-dose combinations. Cancer death was defined as leading cause of death = malignant neoplasm; non-cancer deaths were censored (cause-specific hazard). Survey-weighted Cox models incorporated strata/PSU and pooled MEC weights (WTMEC2YR/10). Models used complete-case covariates per model. Results: Among 56,253 adults (1,850 cancer deaths), baseline PPI use was associated with higher cancer-specific mortality in unadjusted analysis and remained elevated after sequential adjustment (Table). Conclusions: PPI use was associated with higher cancer-specific mortality in a nationally representative U.S. cohort. These findings support careful review of PPI indication and duration and reinforce deprescribing when PPIs are not clearly indicated. Residual confounding remains possible, warranting studies using designs that better address this bias. Sequentially adjusted survey-weighted Cox models estimating the cause-specific hazard of cancer death associated with PPI use (NHANES 1999–2018). Model N Events HR (CI) Model 0: Unadjusted 56253 1850 2.63 (2.21 - 3.12) Model 1: +Age +Sex 56253 1850 1.36 (1.14 - 1.62) Model 2: +Race +PIR 51140 1695 1.40 (1.17 - 1.68) Model 3: +Diabetes +Hypertension +HLD 51140 1695 1.40 (1.18 - 1.67) Model 4: +log(cotinine)+log(metals) 9538 407 1.45 (1.10 - 1.91) PIR = Poverty Income Ratio. HLD = Hyperlipidemia. Metals = lead, cadmium, mercury. HRs represent cause-specific hazards for cancer death; non-cancer deaths were treated as censoring events.

Predictors of EGFR-mutant primary lung adenocarcinoma.

10591 Background: The proportion of lung cancer cases in individuals who have never smoked (INS) is increasing. Most of these cases are adenocarcinoma (AC) harboring Epidermal Growth Factor Receptor (EGFR) mutations. As predictors of AC and mutational status (EGFR positive [EGFRp] vs EGFR negative [EGFRn]) are incompletely elucidated, we sought to identify demographic, clinical, and imaging predictors of EGFRp AC. Methods: Data were obtained from Weill Cornell’s Lung Cancer Database, integrating EGFR mutation status derived from genomic testing, validated natural language processing of unstructured clinical data, and individual and area-level predictors from a large New York City health system. We included patients with early stage, surgically resected primary lung AC, allowing for uniform, robust pathologic and genomic characterization. Lesions were identified on computed tomography (CT) prior to diagnosis The primary outcome was EGFR positivity. LASSO-penalized logistic regression with 10-fold cross-validation was used to identify key predictors in high-dimensional, correlated data. Model performance was evaluated using cross-validated AUC and classification accuracy. Results: Among 1145 adults with primary lung AC (312 subsolid nodules [SSNs] and 833 solid nodules; mean age 69.9 [SD, 9.6]), 58.1% were female and 75.4% had a history of smoking. EGFRp ACs (vs EGFRn) were more likely to present as SSNs (39.3% vs 21.7%, p&lt;0.001) and occur in women (63.6% vs 55.7%, p=0.013), Asian patients (32.7% vs 8.4%, p&lt;0.001), and INS (44.9% vs 15.3%, p&lt;0.001). Those with EGFRp AC were less likely to meet USPSTF lung cancer screening (LCS) criteria (12.5% vs 36.0%, p&lt;0.001) and had lower prevalence of chronic obstructive pulmonary disease, other pulmonary disease, and weight loss at presentation; p&lt;0.05. LASSO-selected predictors of EGFR positivity included SSN density and &gt;1 SSN on CT, former smoking status, family history of LC, and higher exposure to ambient air pollutants (PM2.5, NO2, O3). The model demonstrated good discrimination (AUC 0.77, 0.77-0.78). In the SSN subgroup, new LASSO-selected features positively associated with EGFR positivity included right middle lobe location and lobulated margins on CT and SO2 exposure. Cystic morphology, reticulation, and a new or growing solid component on CT were inversely associated with EGFR positivity. Conclusions: In a robust genomically linked and clinically, radiologically, and environmentally enriched dataset, we identified distinct demographic characteristics (female sex, Asian race, family history of LC), CT features (SSN density, multiplicity, lobulated margins), and environmental exposures (PM2.5, NO2, O3, SO2) that may predict EGFR positivity. Moreover, three-fold fewer adults with EGFRp AC met USPSTF LCS criteria. These findings support integrating imaging and non-tobacco risk factors to inform lung AC risk stratification, genomic testing, and more inclusive screening strategies.

Inpatient outcomes by socioeconomic characteristics among younger adults hospitalized with gastrointestinal malignancies in the United States, 2018–2022.

e23168 Background: Early-onset gastrointestinal (GI) cancers are increasingly recognized, yet national data describing inpatient outcomes and socioeconomic differences among younger adults remain limited. Methods: A serial cross-sectional, survey-weighted analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations among younger adults (age &lt; 50 years) with a principal diagnosis of GI malignancy were identified. Socioeconomic exposures included primary payer and neighborhood income quartile. Outcomes included in-hospital mortality (primary), length of stay (LOS), hospitalization cost estimated using cost-to-charge ratios, and discharge to facility. National estimates accounted for survey weighting, clustering, and stratification. Multivariable survey-weighted logistic and linear regression models adjusted for age, sex, race, cancer subtype, calendar year, elective admission status, APR-DRG severity, hospital teaching status, geographic region, payer, and income quartile. Results: The cohort included 21,775 unweighted admissions, representing an estimated 108,875 hospitalizations nationally. Overall in-hospital mortality was 2.19%. After adjustment, Medicare coverage was associated with higher in-hospital mortality compared with private insurance (odds ratio [OR] 5.38, 95% CI 1.67–17.34), while elective admission was associated with lower mortality (OR 0.59, 95% CI 0.35–0.99). Illness severity demonstrated the strongest association with outcomes; each one-unit increase in APR-DRG severity was associated with higher mortality (OR 5.20), longer LOS (+3.18 days), and higher hospitalization cost (+$9,293). Complicated hospitalizations were associated with longer LOS (+5.10 days) and higher costs (+$38,211). Hospitalization costs increased significantly in 2020 compared with 2018 and remained elevated through 2022. Conclusions: Among younger adults hospitalized with GI malignancies, inpatient outcomes were most strongly associated with illness severity and payer status rather than neighborhood income. These nationally representative findings provide benchmarking data on socioeconomic patterns in inpatient outcomes for early-onset GI cancer hospitalizations.

Association of acute myeloid leukemia (AML) patient, disease, and molecular characteristics with a long-term (LT) response to olutasidenib.

6523 Background: Mutations in isocitrate dehydrogenase 1 (m IDH1 ) occur in 7%-14% of patients with AML. Olutasidenib is a potent, oral small-molecule mIDH1 inhibitor that selectively inhibits IDH1 variants but preserves wild-type IDH1 function. The registrational phase 2 trial (NCT02719574) of olutasidenib in patients with relapsed/refractory (R/R) m IDH1 AML reported a complete remission (CR)/CR with partial hematologic recovery (CRh) rate of 35% and a median CR/CRh duration of 25.3 mo. This analysis examines patient, disease, and molecular characteristics of patients with a LT CR/CRh response to olutasidenib without transplant. Methods: Adults with R/R m IDH1 AML treated with olutasidenib 150 mg twice daily who had a CR/CRh and a duration of response (DOR) &gt;12 mo were included. Overall survival (OS), DOR, event-free survival (EFS), and adverse events (AEs) were assessed. Univariate and multivariate logistic regression analyses were used to examine baseline factors that predicted DOR &gt;12 vs ≤12 mo. Results: Of 147 evaluable patients, 51 (35%) achieved a CR/CRh; of these, 32 (63%) maintained a CR/CRh &gt;12 mo. Excluding 6 patients who proceeded to transplant, 26 (51%) had a DOR &gt;12 mo (Table). Among these patients at baseline, median age was 72 y; 69% were female; 73% had an R132C mutation; 12% had prior venetoclax; 88% were platelet transfusion independent (TI); 73% were red blood cell (RBC) TI. Patients had a median (range) of 2 (0, 5) comutations, most commonly DNMT3A (n=6) or NPM1 (n=5); 2 patients with NPM1 also had FLT3 mutations. Median (95% CI) time to response was 1.9 (1.0, 1.9) mo. Median OS and EFS were not reached. Estimated 48-mo OS was 74% (95% CI: 51%, 88%). Estimated 48-mo EFS was 69% (95% CI: 47%, 83%). 5 (19%) patients relapsed (including 1 after 24 mo); 10 (38%) patients were on treatment at data lock. Significant predictors of response &gt;12 vs ≤12 mo by multivariate analysis were relapsed AML vs refractory AML (odds ratio [OR]: 0.19) and female sex (OR: 0.21). Age, number of comutations, m IDH1 variant, RTK pathway mutations, number of prior therapies, and baseline TI were not significant predictors. Common AEs were nausea (35%), increased ALT, asthenia, constipation, and cough (31% each). Common grade ≥3 AEs were increased ALT, gamma glutamyltransferase increased (19% each), and RBC count decreased (15%). 9 (35%) patients experienced grade ≥3 all-cause AEs after 12 mo (only 1 AE in &gt;1 patient [Coronavirus infection]). Conclusions: Olutasidenib enabled LT CR/CRh in half of R/R m IDH1 AML patients with CR/CRh without transplant (longest response &gt;54 mo). Multivariate analysis identified relapsed (vs refractory) AML and female sex but not baseline TI or molecular factors as a significant predictor of LT response with olutasidenib. Clinical trial information: NCT02719574 . Patients with LT response. DOR Group Patients, n (%) &gt;12 mo 26 (100) &gt;24 mo 19 (73) &gt;36 mo 15 (58) &gt;48 mo 5 (19)

Comparative risk of osteopenia, osteoporosis, and pathological fractures in breast cancer patients treated with steroidal versus non-steroidal aromatase inhibitors: A large-scale real-world data analysis.

e12683 Background: Aromatase inhibitors (AIs) are widely used in hormone positive breast cancer. They are classified as either steroidal or non-steroidal. While both classes are associated with accelerated bone loss and increased risk of osteopenia, osteoporosis, and fractures, direct comparative data on bone outcomes between these classes remains limited. To address this gap, we conducted a large-scale real word analysis to clarify differential bone risks in breast cancer patients treated with different aromatase inhibitors. Methods: This TriNetX analysis utilized 157 healthcare organizations in the Global Collaborative Network. Two cohorts of breast cancer patients initiating non-steroidal (anastrozole/exemestane) versus steroidal (letrozole/fadrozole) aromatase inhibitors were identified. Index events were defined by AI initiation after cancer diagnosis, with outcomes measured from one year post-index onward. Osteopenia, osteoporosis, and pathological fracture diagnoses were analyzed using risk ratios, odds ratios, and survival analyses. Propensity score matching balanced demographics and baseline characteristics, producing 128,276 matched patients in each cohort. Outcomes were analyzed using association measures and Kaplan–Meier survival functions, including all patients irrespective of prior outcomes. Results: After matching, non-steroidal AI users showed higher osteopenia risk (26.1% vs. 23.5%; OR 1.15, p &lt; 0.001) and osteoporosis risk (18.1% vs. 16.4%; OR 1.13, p &lt; 0.001) compared with steroidal AI users. Survival analyses revealed minimal differences (HR ≈ 1.0). Conversely, pathological fractures were slightly less frequent among non-steroidal users (2.5% vs. 2.7%; OR 0.95, p = 0.038; HR 0.84, p &lt; 0.001). Median survival durations for bone outcomes were broadly similar between cohorts. These data suggest non-steroidal AIs may confer slightly greater risks for bone density loss, while steroidal AIs may slightly increase pathological fracture likelihood, though absolute differences appear clinically limited. Conclusions: In this large real-world cohort, non-steroidal aromatase inhibitor users exhibited modestly higher rates of osteopenia (26.1% vs 23.5%, OR ≈ 1.15) and osteoporosis (18.1% vs 16.4%, OR ≈ 1.13) compared with steroidal AI users, while time-to-event differences were minimal. Surprisingly, pathological fractures were slightly less frequent among non-steroidal users (OR 0.95, HR 0.84). These findings are broadly compatible with literature suggesting exemestane (a steroidal AI) may be somewhat less deleterious to bone than non-steroidal agents, though the paradoxical fracture result merits cautious interpretation in light of possible confounding.