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Assessing risk and benefit of adjuvant therapy in stage IB NSCLC.
e20036 Background: The role of adjuvant treatment in stage IB non–small cell lung cancer (NSCLC) remains controversial. In most patients without high-risk features, active surveillance is the standard strategy following resection. However, for patients with high-risk features, the decision between adjuvant treatment (chemo-immunotherapy (CIO) or chemotherapy (CTX)) and surveillance remains unclear. While immunotherapy entered the lung cancer landscape in 2017, the NCCN guidelines still provide only category 2A recommendations in this context, reflecting the absence of definitive evidence. This study revisits the ongoing debate on the optimal management of this subgroup. Methods: We conducted a retrospective cohort study using the SEER Research Plus database and analyzed patients diagnosed with stage IB NSCLC between 2018–2022. Eligible cases had at least one high-risk feature: vascular invasion, visceral pleural involvement, or unknown nodal status (Nx). Non-primary tumors, cases outside the study window, or missing survival time were excluded, leaving 3,185 patients. Patient demographics and clinical variables were extracted. Overall survival (OS) was measured from diagnosis to death or last contact. Kaplan–Meier curves and log-rank tests assessed unadjusted survival, and multivariable Cox proportional hazards regression estimated hazard ratios (HR) with 95% confidence intervals (CI), adjusting for clinically relevant covariates. Analyses were performed in SEER*Stat (v9.0.41.4) and R (v2025.05.1, RStudio). Results: Among the 3,185 patients, 547 received adjuvant treatment (CIO/CTX), while 2,634 did not. Median age at diagnosis was 70 years; 56% were female, 75% non-Hispanic White, and 57% married; most (88%) resided in urban areas (Table 1). Five-year OS was almost identical between groups (70.3% CIO/CTX vs. 72.5% No CIO/CTX; p = 0.22). Multivariable analysis showed no significant association between adjuvant treatment and mortality reduction (HR 1.12, 95% CI 0.89–1.39). Notably, male sex and rural residence were independently associated with worse survival ( p < 0.05). Conclusions: In this SEER-based analysis, adjuvant treatment (CIO/CTX) did not confer a survival advantage over surveillance in patients with stage IB NSCLC and high-risk features, highlighting the need for prospective randomized studies to clarify the role of adjuvant treatments, especially CIO, in this population. Multivariable Cox proportional hazards analysis for overall survival. HR 95% CI P value Diagnosis year 0.91 (0.84, 0.98) 0.02 Age, years 1.05 (1.04, 1.06) <0.001 Marital status (Married) Single 1.16 (0.99, 1.36) 0.06 Setting (Rural) Urban 0.72 (0.58, 0.89) 0.002 Sex Male 1.58 (1.35, 1.85) <0.001 Chemotherapy (None/Unknown) Yes 1.12 (0.89, 1.39) 0.3 Race (NH-White) NH-Black 1.17 (0.90, 1.53) 0.2 Hispanic 0.89 (0.64, 1.24) 0.5 Other 0.65 (0.48, 0.88) 0.005
Protocol for ADHERE: A randomised controlled trial evaluating a digital exercise intervention with virtual supervised group exercise sessions compared to standard of care for patients receiving androgen deprivation therapy for prostate cancer.
TPS5132 Background: In the UK, supervised exercise is recommended by NICE for prostate cancer patients receiving androgen deprivation therapy (ADT); however, engagement in physical activity remains limited. Although high adherence is observed during supervised exercise, it is unclear whether participants maintain activity after supervision. Barriers include treatment-related side-effects and low motivation. Digital exercise interventions that include education and behaviour change support may address these barriers and promote sustained engagement in physical activity. Methods: The primary objective of ADHERE is to determine whether a digital exercise intervention incorporating virtual group exercise sessions improves adherence to physical activity compared with standard of care (SOC). Secondary and exploratory objectives include assessment of health-related quality of life (HRQoL), fatigue, physical function, clinical biomarkers and participant experiences, and evaluation of cost-effectiveness. ADHERE is a single-centre, phase III, two-arm randomised controlled trial. Prostate cancer patients within eight weeks of starting ADT and planned for radiotherapy will be recruited at The Royal Marsden NHS Foundation Trust. Participants will be randomised 1:1, stratified by ADT duration (≤6 months or >6 months), to SOC alone or SOC plus the digital exercise intervention. The intervention includes virtual supervised group exercise sessions delivered weekly over 26 weeks, access to exercise videos, an individualised exercise programme, educational content and “patient buddy” support. Assessments will be conducted at baseline and three, six, and 12-months post-radiotherapy. Primary endpoint is adherence to physical activity guidelines at six months post-radiotherapy, assessed using device-based activity monitor and self-reported exercise diary. Secondary endpoint is HRQoL and will be measured using FACT-P. 160 participants (80 per arm) will be recruited allowing for 20% dropout. ADHERE has ethical and regulatory approval and will be conducted in accordance with Good Clinical Practice. Recruitment for this trial started in December 2025. An interim analysis will be conducted, with final analyses performed following completion of all participant follow-up. Results will be disseminated via peer-reviewed publications and conferences. Clinical trial information: NCT07243834 .
Impact of primary tumor location on treatment and outcomes in Ewing sarcoma.
e23507 Background: Ewing sarcoma is an aggressive primary bone malignancy that arises in various anatomic locations. While treatment typically involves multimodal therapy including chemotherapy, surgery, and radiation, it remains unclear whether anatomic location impacts surgical feasibility, treatment approach, and outcomes. This study evaluated the association between anatomic location and surgical and oncologic outcomes in patients with Ewing sarcoma. Methods: We performed a retrospective cohort study of 46 patients with Ewing sarcoma treated at a single institution. Patients were stratified by primary tumor location: lower extremity (n = 30, 65%), pelvis (n = 12, 26%), and upper extremity (n = 4, 9%). A secondary analysis evaluated extremity subgroups (proximal, middle, distal). Outcomes included surgical approach (limb salvage, amputation, or non-operative), radiation therapy utilization, margin status, complications, local recurrence, metastatic presentation, and mortality. Results: Anatomic location significantly influenced treatment strategy. Pelvic tumors were more likely to receive neoadjuvant radiation compared with lower extremity tumors (41.7% vs 0%, p = 0.001) and were less likely to undergo surgical resection (41.7% vs 90.0% limb salvage, p = 0.006). Upper extremity tumors had the highest rate of adjuvant radiation (50.0% vs 6.7% lower extremity, p = 0.042). All surgical patients achieved negative (R0) margins. Pelvic tumors demonstrated worse oncologic outcomes, including higher mortality (41.7% vs 16.7% lower extremity), higher rates of metastatic disease upon presentation (33.3% vs 13.3%), and increased wound complications (40% vs 11%), though these differences did not reach statistical significance. Lower extremity tumors achieved the lowest mortality (16.7%) with upper extremity tumors exhibiting a 50% mortality rate, although limited by a small sample size (n = 4). Extremity subgroup analysis (proximal n = 20, distal n = 11, middle n = 3) demonstrated proximal tumors had highest implant failure (33.3% vs 9.1% distal) while distal had highest metastatic presentation (27.3% vs 10.0% proximal). Overall cohort characteristics: mean age 21.4 years, mean tumor size 8.0 cm, mean follow-up 80.8 months, overall mortality 26.1%. Conclusions: Primary tumor location significantly impacts treatment approach and demonstrates meaningful trends toward differential outcomes in Ewing sarcoma. Pelvic tumors require more aggressive multimodal therapy, are less frequently resectable, and are associated with higher complications and poorer survival. In contrast, lower extremity tumors achieve highly successful limb salvage rates and favorable survival. These findings highlight the importance of anatomic location in treatment planning, risk stratification, and patient counseling for those with Ewing sarcoma.
Reporting of sex-related data in landmark phase III solid tumor trials presented at ASCO 2025.
11088 Background: Sex-related differences may influence cancer biology, treatment efficacy, and toxicity. Although consideration of sex as a biologically relevant variable is increasingly encouraged in oncology research, the extent to which sex-specific information is visible at the time of initial presentation of practice-changing clinical trial results remains unclear. Methods: We conducted a cross-sectional review of phase III solid tumor trial abstracts enrolling mixed-sex populations presented at the ASCO Annual Meeting 2025. Plenary, oral, and rapid oral abstracts representing practice-changing studies across tumor types and treatment modalities were included. Abstracts were systematically assessed for reporting of sex distribution and for sex-stratified efficacy or toxicity outcomes. Results: Ten landmark phase III trials across gastrointestinal, lung, genitourinary, head and neck, and melanoma cancers were included. Female representation was reported in 1 of 10 abstracts (10%). None of the abstracts reported sex-stratified efficacy analyses, and none reported sex-stratified toxicity outcomes. The absence of sex-specific reporting was consistent across tumor types, therapeutic classes, and session formats, including plenary presentations. Conclusions: Among landmark phase III solid tumor trials presented at ASCO 2025, sex-specific reporting was largely absent at the abstract level, including in practice-changing studies. Limited visibility of sex-specific data at abstract presentation may constrain clinical interpretation and highlights an opportunity to improve reporting practices in oncology trials.
Somatic and actionable genomic alterations in early-onset colorectal cancer versus late-onset disease: Experience from a western Florida tertiary referral center.
e15718 Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing, yet its molecular and therapeutic landscape remains incompletely characterized. We compared somatic mutation profiles and the prevalence of clinically actionable, tissue-agnostic genomic alterations between EOCRC and late-onset colorectal cancer (LOCRC) to assess whether EOCRC represents a biologically distinct entity with differing therapeutic implications. Methods: We retrospectively analyzed next-generation sequencing data from patients with colorectal cancer who presented to Moffitt Cancer Center between 2011-2025, reflecting a large tertiary referral population in Western Florida. Patients were stratified by age at diagnosis as either EOCRC (< 50 years, n = 140) or LOCRC (> 65 years, n = 392). Frequency of somatic mutations and targetable genomic alterations were assessed, including biomarkers that inform eligibility for approved tissue-agnostic or molecularly directed therapies. Comparisons between cohorts were performed using chi-square or Fisher’s exact tests as appropriate, with significance defined as p < 0.05. Results: The median age of the EO cohort was 44 at time of NGS compared to 74 in the LO cohort. The EO group demonstrated higher frequencies of classic CRC driver mutations, including TP53 (81.4% vs 70.9%, p = 0.0077) and APC (79.3% vs 70.9%, p = 0.028). The EO cohort was significantly enriched in alterations affecting DNA damage repair including ATM (14.3% vs 7.7%, p = 0.036), BRCA2 (15.0% vs 5.2%, p = 0.0001), POLE/POLD1 (11.4% vs 2.3%, p = 0.0001) as well as ERBB2 mutations (10% vs 4.8%, p = 0.015). BRAF mutations were more frequent in the LOCRC cohort (11.2% vs 5.0%, p = 0.016) as were incidences of BRAF V600E in RAS wild-type disease (p < 0.0001), suggesting greater eligibility for BRAF-targeted therapy. MSI-high tumors were more common in LOCRC (6.6% vs 2.1%, p = 0.029). TMB-high tumors and KRAS G12C occurred at similar frequencies between cohorts. Patients from the EO cohort were significantly more likely to be enrolled in clinical trials (21.4% vs 4.04%, p < 0.0001). Conclusions: EOCRC and LOCRC exhibit distinct somatic mutation profiles and clinically actionable genomic landscapes. EOCRC is characterized by classic colorectal oncogenic drivers and alterations affecting DNA damage repair. LOCRC demonstrates a higher prevalence of alterations associated with immune responsiveness and pathway-directed therapies, including MSI-H, and BRAFV600E. These molecular differences underscore the importance of comprehensive genomic profiling and support the application of tissue-agnostic and molecularly targeted treatment strategies in colorectal cancer.
Evaluation of survival after chemo-immunotherapy in veterans with extensive-stage small cell lung cancer and brain metastases.
8110 Background: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with rapid progression and poor long-term survival. For decades, platinum–etoposide chemotherapy has produced high initial response rates, but relapse is nearly universal. The addition of atezolizumab or durvalumab to first-line chemotherapy is now standard of care based on improved survival in the IMpower133 and CASPIAN trials, with reported OS 12.3 and 13 months, respectively. However, these pivotal trials enrolled highly selected populations and largely excluded patients with active brain metastases, limiting generalizability. Veterans are particularly underrepresented in clinical trials due to comorbidities and performance status, leaving the real-world effectiveness of chemo-immunotherapy and immune biomarkers in this population poorly defined. Methods: We conducted a retrospective cohort study of Veterans with ES-SCLC treated with first-line chemotherapy alone or chemo-immunotherapy within the Veterans Affairs (VA) health system. Overall survival (OS) was assessed using Kaplan–Meier methods and Cox proportional hazards models in propensity-matched cohorts. Prespecified subgroup analyses evaluated whether treatment effects differed by brain metastasis status. Exploratory analyses also assessed the prognostic association between baseline absolute neutrophil-to-lymphocyte ratio (ANC/ALC) and survival. Results: In the matched overall cohort (n = 1,250), chemo-immunotherapy significantly improved OS compared with chemotherapy alone (median OS 8.88 vs 7.44 months; HR 0.75, p < 0.0001). Among patients who received chemo-immunotherapy (n = 625), 87.0% were treated with atezolizumab and 9.6% with durvalumab. For patients with brain metastases at diagnosis (n = 312), chemo-immunotherapy significantly improved survival (median OS 8.76 vs 5.52 months; HR 0.57, p < 0.0001). An elevated pre-treatment absolute neutrophil count (ANC) to absolute lymphocyte count (ALC) ratio > 2.5 was independently associated with worse survival in both chemo-immunotherapy (HR 1.35, p = 0.013) and chemotherapy-only (HR 1.47, p = 0.0004) groups. Conclusions: This study represents the largest real-world cohort of Veterans with ES-SCLC and demonstrates a significant overall survival benefit with chemo-immunotherapy. The benefit was particularly pronounced among patients with brain metastases, a group historically underrepresented in clinical trials. Elevated ANC/ALC was identified as a potential prognostic biomarker associated with poor outcomes regardless of treatment. Notably, overall survival in our Veteran cohort remained substantially lower than in registrational trials, highlighting the urgent need for future studies with broader eligibility criteria that better reflect real-world populations.
Targeting TP53 pathologic variants for cancer immunotherapy using a self-replicating mRNA vaccine strategy.
3085 Background: TP53 pathogenic variants (PVs) are highly prevalent in human malignancies as a whole and especially in patients with pancreatic ductal adenocarcinoma (PDAC). Approximately 80% of TP53 PVs are missense mutations that may be targeted for cancer therapy. Methods: We have developed a self-replicating mRNA (srRNA) vaccine (TMG-mut TP53 srRNA SA-LNP) encoding concatenated p53 mutant peptides encompassing 14 hotspot TP53 missense mutations in PDAC, encapsulated in sialic acid (SA)-modified lipid nanoparticles (LNPs). These 14 hotspot TP53 PVs were selected by examining four public available datasets and from our previous studies. Results: TMG-mut TP53 srRNA SA-LNPs incorporated Venezuelan equine encephalitis virus replicase which enabled higher and prolonged in vivo protein expression compared to conventional mRNA construct. Encapsulation with SA-modified LNPs led to significantly better efficiency in targeting dendritic cells (DCs) in vitro and in vivo compared to conventional LNPs. We used in vitro (cell lines) and in vivo assays (PDX and human engineered mouse genetic models) to test the efficacy of our RNA vaccine. We validated the detection of TP53 neoantigen by mass spectrometry generated by our srRNA vaccine. We then tested its anti-tumor immunity by itself alone and in combination with anti-PD1 inhibition using multiple cell lines and PDX that carry different TP53 PV (R175H and R273H). TMG-mut TP53 srRNA SA-LNP stimulated potent and specific anti-tumor CD8 + T cell responses in in vitro and in vivo assays using autologous DCs, T cells and cancer cells from multiple PDAC patients. Using both Panc02 syngeneic PDAC cell line and patient-derived PDAC xenografts (PDX), we show that TMG-mut TP53 srRNA SA-LNP stimulated potent and specific anti-tumor immunity against PDAC tumors that harbor different corresponding p53 PVs. Panc02- TP53 R175H tumor-bearing transgenic mice expressing human HLA-A*02:01 treated with TMG-mut TP53 srRNA SA-LNP showed significantly suppressed tumor growth and prolonged survival with increased tumor infiltration of activated CD8 + T cells as well as increased production of cytokines including type II interferon, TNFalpha, and other biomarkers. We also show our vaccine stimulates increased tumor cell apoptosis. In addition, TMG-mut TP53 srRNA SA-LNP dramatically enhanced the anti-tumor immunity of anti-PD1 by synergistically suppressing tumor growth and prolonging the survival of tumor-bearing mice in both low and high-tumor burden animal model. Conclusions: Our results demonstrate for the first time that missense p53 PVs are valid targets for developing novel cancer immunotherapy using srRNA vaccine approach enhanced by SA-LNPs encapsulation. Our data potentially opens a new approach for developing mRNA vaccine-based immunotherapy for a large population of cancer patients as TP53 PVs are highly prevalent in nearly every type of malignant tumors.
National trends, disparities, and inpatient outcomes in appendiceal adenocarcinoma: A U.S. nationwide analysis, 2016–2021.
e23356 Background: Appendiceal adenocarcinoma is a rare gastrointestinal malignancy with heterogeneous inpatient management ranging from limited resection to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Large, contemporary population-level data examining inpatient management patterns and disparities are lacking. We evaluated national trends, treatment utilization, and demographic disparities among adults hospitalized with appendiceal adenocarcinoma in the United States. Methods: We analyzed the Nationwide Inpatient Sample (2016–2021) to identify adult hospitalizations with a principal diagnosis of malignant neoplasm of the appendix, applying survey weights for national estimates. Management strategies were classified as appendectomy, right hemicolectomy, CRS/HIPEC, or no surgery. CRS/HIPEC was identified using procedural codes, acknowledging potential under-capture in administrative data. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay (LOS), prolonged hospitalization (≥90th percentile), and inflation-adjusted hospital costs. Multivariable survey-weighted regression models adjusted for demographics, socioeconomic status (SES), comorbidity burden, illness severity, admission type, hospital characteristics, procedure type, and year. Results: An estimated 17,115 hospitalizations were identified, increasing by 26% from 2016 to 2021 (P < 0.001). Overall in-hospital mortality was 1.5%. After adjustment, female sex was associated with lower odds of mortality, while Black race and higher SES were associated with higher adjusted odds of mortality, potentially reflecting referral patterns and case complexity. Median LOS was 5 days, with most admissions lasting ≤5 days. Total inflation-adjusted inpatient costs exceeded $1.7 billion, with disproportionate costs driven by surgical admissions and prolonged hospitalizations. Right hemicolectomy was the most common intervention (52%), whereas CRS/HIPEC was captured in 13% of hospitalizations, acknowledging potential under-representation in administrative data. No significant demographic differences were observed in adjusted odds of undergoing appendectomy or hemicolectomy. Conclusions: Hospitalizations for appendiceal adenocarcinoma increased substantially from 2016 to 2021, while inpatient mortality remained low but varied across demographic groups. Inpatient care was associated with substantial resource utilization, and CRS/HIPEC was infrequently recorded in this national cohort. These findings highlight rising inpatient burden and demographic variation in outcomes, supporting the need for optimized referral pathways and equitable access to specialized care.
Understanding the awareness-to-enrollment gap: An assessment of oncologist barriers in clinical trial accrual.
e13689 Background: Adult cancer clinical trial accrual remains critically low. Physician awareness is vital to increasing enrollment, yet trial discovery is often time consuming and disconnected from clinical workflows. As part of an NCI SBIR-funded project to integrate AI trial-matching into theMednet, a platform specifically designed to engage community-based oncologists, we sought to characterize oncologist trial searching behaviors and unmet needs. Methods: We surveyed oncologist users of theMednet.org to assess trial awareness, frequency of trial consideration during clinical care, enrollment activity and satisfaction with current trial discovery tools using a 5-point Likert scale. Participants will be resurveyed after 6 months of exposure to an AI platform that matches patient cases to appropriate clinical trials. Data were analyzed using descriptive statistics. Results: Respondents (n = 294) included medical (41%) radiation (46%), pediatric (6.5%) and gynecologic (5.4%) oncologists across academic (43%) and community (50%) settings. Seventy-seven percent of oncologists expressed confidence in discussing trials and 54% reported high awareness of clinical trials; 60% frequently consider trials during routine care. Consideration of trials strongly correlated with enrollment (Spearman’s ρ = 0.645, p < 0.001). Barriers emerged in trial discovery with only 42% reporting ability to identify trials efficiently. While a majority report using online tools (ClinicalTrials.gov, institutional databases) to search for trials, only 35% rate them as useful. Major barriers include finding appropriate trials (65%), logistical/practice barriers (64.3%) and time constraints (47.6%). Significant baseline disparities were observed between academic and community settings regarding awareness and enrollment, though readiness for AI-driven solutions was high across both groups (Table 1). Conclusions: Oncologists lack efficient discovery tools, particularly in community settings where 85% of patients receive care. Existing digital resources are widely used but poorly rated. Our data suggest the primary barrier is not a lack of interest, but a lack of effective tools. To bridge this gap, theMednet has developed an embedded AI trial matching platform designed to surface trials to physicians at the point of care. By leveraging theMednet’s extensive community reach, this intervention aims to reduce discovery barriers and democratize trial access for all patients. Future work will evaluate platform usability and impact on enrollment. Baseline trial behaviors by oncology practice setting. Academic (n=125) Community (n=148) p-value Trial Awareness (Mean Likert) 3.92 3.31 <.001 Trial Consideration (Mean Likert) 4.06 3.40 <.001 Zero Enrollments (Past 6 months) 16% 31.8% 0.001 Readiness for AI-Trial Matching Tool 90.4% 88.5% 0.82
A multicenter randomized phase II trial assessing the efficacy and safety of mCapOX plus cetuximab with mFOLFOX6 plus cetuximab as first-line treatment for <i>RAS/BRAF</i> wild-type metastatic colorectal cancer: Updated results from the CAPCET study.
3598 Background: The CAPCET study was designed to assess the efficacy and safety of modified capecitabine and oxaliplatin (mCapOX) plus cetuximab (CET) and modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus cetuximab (CET) for the first-line treatment of left-side unresectable RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods: CAPCET was an open-label, randomized, multicenter, phase II non-comparative trial (NCT05022030). Patients with unresectable RAS/BRAF wt mCRC from 20 China centers were randomly assigned (1:1) to receive up to 12 cycles biweekly mCapOX (capecitabine 1000mg/m 2 twice daily on Day 1-7 and oxaliplatin 85 mg/m 2 on Day 1) plus CET (500mg/m 2 ) (arm A) or mFOLFOX6 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , fluorouracil 400mg/m 2 on day 1, and fluorouracil 2400 mg/m 2 over 46h) plus CET (500mg/m 2 ) (arm B) followed by maintenance (either capecitabine plus CET or capecitabine alone at the discretion of the investigators) or treatment-free intervals until progression on treatment, toxicity, or death. The primary endpoint was progression-free survival (PFS) rate at 9 months. This is an updated result with a median follow-up of 26.1 months and cost-effectiveness evaluation. Results: Between September 2021 and April 2024, 168 patients were enrolled in the intention-to-treat (ITT) population and 156 patients were included in the per-protocol (PP) population. In the ITT population, the 9 months-PFS rates were 67.9% (95% CI 58.6%-78.6%) in arm A and 61.9% (95% CI 52.3%-73.2%) in arm B, and the primary endpoint was met. The median PFS (arm A/B) was 11.6 months/10.8 months (P=0.183). The overall response rate (ORR) and disease control rate (DCR) in arm A were higher than those in arm B with 64.3% versus 56.0% and 90.5% versus 84.5%, respectively. The 2-year overall survival (OS) rate (arm A/B) was 75.8% vs 68.6%. The median OS was not reached in the arm A while it was 35.5 in the arm B. Grade≥3 adverse events (AEs) occurred in 26.1% of patients, with 15.0% in arm A and 37.0% in arm B. The most commonly Grade≥3 AEs was neutropenia, rash, and leukopenia and there were no grade 5 AEs reported. A cost-effectiveness analysis showed an incremental cost-effectiveness ratio of $19,067 per QALY for mCapOX + CET, below the Chinese willingness-to-pay threshold ($ 41,188/QALY). Conclusions: The CAPCET study met its primary endpoint. mCapOX + CET demonstrated higher ORR/DCR and 2-year OS, with reduced toxicity, compared to mFOLFOX6 + CET. These findings support mCapOX + cetuximab as a clinically effective, better-tolerated, and cost-effective first-line treatment for left-sided RAS/BRAF wild-type mCRC within the Chinese economic framework, providing rationale for ongoing phase III evaluation (NCT06616259). Clinical trial information: NCT05022030 .
Demonstrating real-time and low-latency quantum error correction with superconducting qubits
Abstract Quantum error correction will be essential for quantum computers to realise their full potential. As quantum computers advance towards demonstrating a universal fault-tolerant logical gate set, implementing scalable and low-latency real-time decoding will be crucial to avoid an exponential slowdown and maintain a fast logical clock rate. Here, we demonstrate low-latency feedback with a scalable FPGA decoder integrated into the control system of a superconducting quantum processor. We perform an 8-qubit stability experiment with up to 25 decoding rounds and a sub-microsecond mean decoding time per round, providing strong evidence that the backlog problem will be avoided when the decoder is operated as a streaming decoder on a superconducting hardware with the strictest speed requirements. We observe logical error suppression as the number of decoding rounds is increased. We also implement and time a fast-feedback experiment demonstrating a decoding response time of 9.6 μ s for a total of 9 measurement rounds.
A phase II trial of trifluridine/tipiracil plus oxaliplatin in patients with advanced or metastatic biliary tract cancer following first-line therapy.
TPS4258 Background: Biliary tract cancers (BTCs) comprising of intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer are aggressive and difficult cancers to treat. Most patients present with metastatic or unresectable disease, and systemic therapy is the only therapeutic option. Treatment options are highly limited after progressing on first line therapy with median survival of 6 months. We demonstrated encouraging activity with single agent trifluridine/tipiracil (FTD/TPI) and FTD/TPI plus irinotecan in separate phase 2 trials in patients with refractory BTCs after multiple lines of therapies (NCT03278106 and NCT04072445). Disease control rate (DCR) of 50% was reported with the combination therapy and median OS was 9.1 months. Prior studies have suggested oxaliplatin-based therapy may be more effective than irinotecan-based therapy in BTC. Thus, FTD/TPI plus oxaliplatin may be an active regimen in patients with advanced BTCs. Methods: This is a phase II trial evaluating FTD/TPI plus oxaliplatin as second line treatment in patients with advanced BTCs and disease progression on standard of care gemcitabine-based combination therapy. Key inclusion criteria are pathologically confirmed BTC, ECOG performance status 0 or 1, prior gemcitabine-based combination therapy, adequate organ function, signed informed consent. Key exclusion criteria include > 1 prior line of systemic therapy for advanced disease (adjuvant therapy not counted) and active autoimmune disease requiring systemic therapy. Participants will be enrolled at Case Comprehensive Cancer Center sites and receive a dose of FTD/TPI of 25 mg/m 2 twice daily on days 1-5 and oxaliplatin 85 mg/m 2 on day 1 of a 14-day cycle until disease progression, intolerable toxicities, or patient declines to continue study. Primary endpoint is DCR, defined as proportion of patients achieving responses or stable disease with trial treatment. The trial is a Simon 2-stage optimal design with a significance level of 0.05 and 80% power. We estimate a DCR of 0.62 compared to historical control of 0.33 in second line setting. If ≤2 patients have disease control out of the first 6 patients enrolled, then regimen will be considered ineffective. If > 3 patients have disease control, then the study will proceed to stage 2. During stage 2, an additional 18 patients will be enrolled for 24 total evaluable patients. If > 12 patients of the 24 evaluable patients have disease control, then the trial will be considered a success and a larger trial will be planned. Secondary endpoints are grade and duration of adverse events, ORR, PFS, OS. Correlative studies are circulating DNA and oral and fecal samples for microbiome testing. The study is supported by the National Comprehensive Cancer Network (NCCN) through a grant provided by Taiho Oncology. Neither NCCN nor Taiho are the sponsor. Clinical trial information: NCT07146646 .
Impact of early tacrolimus levels on survival outcomes following allogeneic hematopoietic stem cell transplantation.
e18563 Background: Tacrolimus is routinely used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (HSCT); however, the prognostic impact of early post-transplant tacrolimus exposure remains unclear. We evaluated the association between tacrolimus levels within 30 days after allogeneic HSCT and survival outcomes. Methods: This is a single-center retrospective study of 72 adult patients who underwent matched related (MR), matched unrelated (MU), or haploidentical allogeneic HSCT between January 2024 and May 2025. For each patient, measurements of tacrolimus exposure within 30 days post-transplant (mean, standard error of the mean [SEM], variance, minimum, maximum, and number of levels <7 ng/mL) were calculated and analyzed for associations with clinical and survival outcomes. Results: The median age was 60 years; 45.8% were male, and 80.6% were White. Donor types included MU (63.9%), MR (6.9%), and haploidentical donors (29.2%). Myeloablative and reduced-intensity conditioning were used in 68.1% and 31.9% of patients, respectively. The mean tacrolimus level was 8.45 ng/mL (SEM 0.19), with a variance of 2.74 and a range of 5.5–13.9 ng/mL. The median number of tacrolimus levels <7 ng/mL was six. Median follow-up was 14 months, and the estimated 1-year overall survival (OS) was 90.1%. On univariate analysis, higher mean tacrolimus levels were associated with inferior OS (OR 1.49, 95% CI 1.00–2.23, p=0.048), but not with acute kidney injury (p=0.30), acute (p=0.39) or chronic GVHD (p=0.21), relapse (p=0.93), 100-day (p=0.10) or 1-year survival (p=0.35), or non-relapse mortality (NRM, p=0.07). Higher SEM was associated with increased NRM (OR 2.68, 95% CI 1.11–6.46, p=0.028) and worse OS (OR 2.36, 95% CI 1.02–5.44, p=0.044). Other tacrolimus metrics, including variance, minimum, or maximum of tacrolimus level and numbers of tacrolimus level <7 ng/ml, were not significantly associated with NRM (p=0.06, p=0.86, p=0.06, p=0.72) or OS (p=0.08, p=0.68, p=0.10, p=0.63), respectively. On multivariate Cox proportional hazards analysis, higher mean tacrolimus level remained independently associated with inferior OS (HR 8.56, 95% CI 1.38–53.13, p=0.02), whereas SEM was not (HR 0.20, 95% CI 0.02–1.70, p=0.14). In a second multivariate model, a mean tacrolimus level >11 ng/mL was significantly associated with worse OS (HR 13.69, 95% CI 1.35–139.03, p=0.03), independent of age, donor type, number of antigen mismatches, conditioning intensity, HCT-CI score, incidence of acute or chronic GVHD, and infection. Conclusions: Higher early tacrolimus exposure, particularly mean levels >11 ng/mL, was independently associated with inferior OS after allogeneic HSCT. Other measures of tacrolimus variability were not significantly associated with survival. Future studies are warranted to clarify the mechanisms underlying these findings.
ctDNA versus PET/CT at end of treatment in large B-cell lymphoma: A diagnostic accuracy meta-analysis.
e19090 Background: PET/CT remains crucial for end-of-treatment (EOT) evaluation in large B-cell lymphoma (LBCL), but low specificity results in unnecessary biopsies and patient discomfort. Circulating tumor DNA (ctDNA)-based minimum residual illness (MRD) may aid in the identification of actual residual sickness. Methods: We conducted a systematic review and meta-analysis of diagnostic accuracy using MEDLINE, Embase, CENTRAL, and Scopus. Eligible studies compared EOT ctDNA-MRD to PET/CT with verified recurrence or long-term remission. The outcomes were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The study's quality was rated using the QUADAS-2 scale. A bivariate random-effects model combined sensitivity and specificity, yielding hierarchical summary receiver operating characteristic (HSROC) curves. Results: Nine studies with a total of 932 participants were included. ctDNA-MRD showed higher specificity (92%, 95% CI 88-95%) and PPV (81%, 95% CI 73-88%) than PET/CT (specificity 68%, 95% CI 60-75%; PPV 46%, 95% CI 38-55%), while maintaining similar sensitivity. The negative predictive value for ctDNA was higher (91%, 95% CI 86-95%) than for PET (79%, 95% CI 72-85%). Combined PET+ctDNA techniques had the highest diagnostic odds ratio and fewer false positives. The results were similar across Deauville criteria and testing systems. Conclusions: ctDNA-MRD has higher specificity and predictive value than PET/CT at EOT in LBCL and significantly improves risk categorization whether used alone or in conjunction with imaging. Clinical Takeaway: Incorporating ctDNA-MRD into EOT assessment can reduce unnecessary biopsies and enable more accurate, confidence-based post-treatment decision-making.
Phase 2 study of ivonescimab in patients with cutaneous squamous cell carcinoma.
TPS9615 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. In the setting of unresectable locally advanced or metastatic disease, checkpoint inhibitors are standard of care and are associated with robust response rates and durable disease control. However, in those who do not respond or progress on immunotherapy, there are limited available standard therapies. Ivonescimab is a tetravalent bispecific antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor A (VEGF-A) that has shown promising activity in multiple tumor types. VEGF-mediated activities include driving angiogenesis creating a tortuous tumor vasculature and decreasing effector T-cells within the tumor microenvironment. Herein, we hypothesize that dual targeting of PD-1 and VEGF-A may overcome resistance to checkpoint inhibitors and extend the benefit of immunotherapy in CSCC. Methods: This phase 2, single-arm study will enroll up to 24 patients and will be conducted using a Bayesian optimal phase 2 (BOP2) design. Prespecified activity goal for the first stage of accrual was met; second stage accrual began in January 2026. Patients will receive Ivonescimab 20mg/kg intravenously every 3 weeks until progression, death, or intolerance. The main inclusion criteria include unresectable locally advanced or metastatic CSCC that is refractory to prior checkpoint inhibitors, Eastern Cooperative Oncology group performance score of 0-1, and measurable disease by RECIST version 1.1. Primary exclusion criteria comprise prior severe immunotherapy-associated toxicities, prior organ transplant, or major blood vessel invasion. There are no limits on lines of therapy. Primary objective and endpoint is objective response rate in CSCC. Key secondary endpoints include duration of response, disease control rate, progression free survival, and safety. Additional exploratory objectives include evaluating predictive biomarkers of treatment response or resistance utilizing a mandatory biopsy performed both pre-and on-treatment, with correlatives including whole exome sequencing, RNA sequencing, multiplex IHC. Active recruitment and enrollment are ongoing at The University of Texas MD Anderson Cancer Center, Houston, Texas. Copyright © 2026 AACR. Originally presented at AACR 2026. Reprinted with permission. Clinical trial information: NCT06567314 .
Remote activity monitoring to detect physical function decline and unexpected medical events in patients with prostate cancer undergoing androgen deprivation therapy.
5084 Background: Among patients with prostate cancer (PC), treatment with androgen deprivation therapy (ADT) is associated with reduced physical function, which can result in diminished quality of life and the occurrence of adverse medical events. The use of wearable activity monitors allows for remote monitoring of daily activity to potentially detect early functional decline and predict significant medical events such as hospitalization, serious adverse events, and premature death. This study evaluated whether wearable activity monitoring could serve as an early indicator of functional decline and impending adverse events in patients with PC undergoing ADT. Methods: PC patients receiving ADT at Cedars-Sinai and Durham VA who enrolled in the DigiPRO trial (NCT04575402) wore a Fitbit Charge over 12 weeks to track quantitative physical activity and sleep data for prediction of the occurrence of unexpected medical events (composite of hospitalization, premature death, or fall) and significant patient-reported physical function decline (> 5 NIH PROMIS T score points) within 6-months follow-up. Results: 40 patients were included in the analysis (median age 70, range 51-87, 37% Black and 63% White; 10% identified as Hispanic). On average, PC patients walked 5,189 steps/day, were sedentary 16 hours/day, and slept 5.8 hours/night. A clinically meaningful decline in daily steps (> 500 steps) within the first 3 months of initiating ADT was associated with higher odds of experiencing an unexpected medical event (hospitalization, death, fall) (OR = 3.03; 95% CI 1.6-5.9, p = 0.001 ) and clinically meaningful decline in patient-reported physical function (> 5 PROMIS T score points) occurring within 6 months from study completion (OR = 5.2, 95% CI; 1.3-11.7, p = 0.02 ). Conclusions: These findings suggest remote activity monitoring may serve as a novel early warning system to identify patients who are at increased risk of unexpected medical events and clinically meaningful physical function decline in PC patients undergoing ADT. Use of this early warning system could lead to targeted interventions in high-risk patients to reduce morbidity and perhaps even prolong survival in patients undergoing ADT. Clinical trial information: NCT04575402 .
Phase 1 basket study of telisotuzumab adizutecan (Temab-A, ABBV-400), a c-Met protein–targeting antibody-drug conjugate: Results from patients with head and neck squamous cell carcinoma (HNSCC).
6027 Background: c-Met protein is expressed in several tumor types, including HNSCC, and is associated with a poor prognosis. Temab-A comprises a c-Met protein-targeting antibody conjugated to a topoisomerase 1 inhibitor. Phase 1 studies evaluating Temab-A monotherapy in solid tumors showed antitumor activity and a manageable safety profile (NCT05029882, NCT06084481). Here, we report on the efficacy and safety of Temab-A in HNSCC. Methods: This phase 1, open-label basket study (NCT06084481) enrolled patients (pts) ≥18 years with histologically/cytologically confirmed locally advanced or recurrent/metastatic, unresectable HNSCC, with Eastern Cooperative Oncology Group performance score ≤1. Pts must have had measurable disease per RECIST v1.1 criteria, and disease progression following ≥1 line of systemic therapy in the advanced/metastatic setting. Pts were platinum-resistant or deemed ineligible/unfit for platinum-based therapy per investigator. Prior checkpoint inhibitor treatment was required, unless contraindicated. Pts received 2.4 or 3.0 mg/kg Temab-A every 3 weeks. Primary objectives were safety and efficacy. Results: As of Sept. 11, 2025, 43 pts with HNSCC received Temab-A. The median age was 64 years (range 20–85). Median number of prior lines of systemic therapy was 3 (range 1–12), and median follow-up was 12 months. Objective response rate (ORR) was 21%; duration of response and overall survival were immature at data cutoff. Efficacy data are shown in the Table. The most common treatment-related adverse events (TRAEs) of any Grade (G) included fatigue (51%), anemia (49%), and nausea (40%). TRAEs G ≥3 occurred in 47% of pts. G ≥3 TRAE occurring in ≥10% of pts was anemia (33%). The adjudicated interstitial lung disease/pneumonitis rate was 9.3% (G1, n=2; G2, n=1; G3, n=1). TRAEs led to treatment discontinuation in 12%, dose interruption in 30%, and dose reduction in 26% of pts. There was 1 TRAE that led to death. Exploratory biomarker analyses are ongoing. Pharmacokinetics of Temab-A in HNSCC were consistent with other tumor types. The half-life of the conjugate and payload was 4 and 13 days, respectively. Conclusions: Temab-A had a manageable safety profile and showed encouraging antitumor activity in advanced HNSCC. Clinical trial information: NCT06084481 . Temab-A efficacy. a Outcome Pts with HNSCC (N=43) Best overall response, n (%)Complete responsePartial responseStable diseaseProgressive diseaseNot assessed b 011 (26)22 (51)7 (16)3 (7) Objective response rate c , n (%)95% CI 9 (21)10, 36 Clinical benefit rate c , n (%)95% CI 33 (77)61, 88 Median progression-free survival, months (95% CI) 4.3 (3.8, 5.4) a Responses were assessed by investigators per RECIST v1.1 criteria. b Pts without postbaseline scan. c Confirmed. CI, confidence interval.
Pemigatinib for untreated unresectable/metastatic cholangiocarcinoma (mCCA) with fibroblast growth factor receptor-2 (FGFR2) rearrangement: Phase 3 FIGHT-302 results.
4017 Background: First-line mCCA treatment is chemotherapy and immunotherapy. Based on the phase 2 FIGHT-202 trial, pemigatinib was the first FGFR1-3 inhibitor approved in second line and beyond for mCCA with FGFR2 rearrangement. Results from the phase 3, randomized, global FIGHT-302 trial evaluating pemigatinib as first-line therapy are reported here (NCT03656536). Methods: Patients (pts) aged ≥18 y with previously untreated mCCA with FGFR2 rearrangement were randomized 1:1 to receive oral pemigatinib (13.5 mg once daily q21) or intravenous chemotherapy (1000 mg/m 2 gemcitabine + 25 mg/m 2 cisplatin d1,8 q21 ≤8 cycles) stratified by previous receipt of 1 chemotherapy cycle, geographic region, and tumor burden. Pemigatinib crossover was allowed for control arm pts progressing on chemotherapy. Primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. Results: After prescreening >4000 pts, only 196 had FGFR2 rearrangement and were screened; 167 were randomized to receive pemigatinib (n=83) or chemotherapy (n=84) before closing the study early due to slow accrual. Baseline characteristics and demographics were similar between arms. Median PFS (mPFS) with pemigatinib versus chemotherapy was 8.3 versus 6.8 mo, respectively (hazard ratio [95% CI], 0.58 [0.39-0.87]; nominal P =.0078); secondary efficacy endpoints generally supported primary results (Table). Median OS was similar, although these results are confounded by FGFR inhibitor administration as second-line treatment. In the crossover group (n=42, second-line pemigatinib), mPFS was 8.1 mo. Safety was consistent with previous results (Table). Exploratory analyses of genetic co-alterations associated with treatment response will be presented. Conclusions: FIGHT-302 was the first phase 3 trial of a targeted therapy for untreated mCCA. Pemigatinb demonstrated superior activity and prolonged mPFS compared with first-line chemotherapy. The results confirm the current management paradigm of pemigatinib administration after disease progression on chemotherapy. Clinical trial information: NCT03656536 . Pemigatinib Gemcitabine + cisplatin mPFS (95% CI), mo a 8.3 (6.5-12.2) 6.8 (6.1-8.3) Objective response rate, n/N (%) a 39/83 (47) 13/84 (15.5) Median duration of response (95% CI), mo a 14.2 (8.7-24.7) 6.3 (4.3-not estimable) Median overall survival (95% CI) a,b , mo 24.4 (18.6-35.9) 25.0 (18.7-34.2) Treatment related TEAEs, n/N c (%) 80/83 (96) 70/73 (96) Serious TEAEs, n/N (%) c,d 23/83 (28) 17/73 (23) Grade ≥3 TEAEs, n/N (%) c 65/83 (78) 49/73 (67) TEAEs leading to treatment discontinuation, n/N (%) c 5/83 (6) 8/73 (11) Fatal TEAE, n/N (%) c,d 3/83 (4) 0 a All randomized pts. b Interpretation limited by second-line treatment with FGFR inhibitor in gemcitabine + cisplatin arm. c Pts who received ≥1 study dose. d None deemed treatment related.
Second-line options in patients with BRAF-negative advanced melanoma following progression on anti-PD-1 therapy: A retrospective observational study from two centers in Russia.
e21519 Background: While anti-PD-1 is the first-line (1L) standard for BRAFwt advanced melanoma (aM), disease progression (PD) occurs in over half of patients, requiring second-line (2L) strategies. The ipilimumab/nivolumab (Ipi/nivo), though frequently used in 2L, is limited by toxicity and financial burden, and its ability to overcome resistance to prior immunotherapy is unclear. We aimed to assess different 2L options and the potential of Ipi/nivo based on prior anti-PD-1 response. Methods: A retrospective observational study approved by the IRB was conducted at two Russian centers: N.N. Blokhin NMRCO and Moscow Oncology City Hospital 62. We included all pts aged ≥18 yrs with BRAFwt aM who progressed on anti-PD-1 and were treated or consulted in these centers in 2023. We assessed the PFS from the start of 2L to PD, OS from the start of 1L (OS1) and 2L (OS2) to death from all pts and PFS, OS1 and OS2 in the Ipi/nivo group regardless of previous best response to anti-PD-1: complete and partial response (CR and PR), stable disease (SD), PD. Results: A total of 86 pts were included, 38 (44,2%) male and 48 (55,8%) female, with a mean age of 61,2 yrs. The 2L options are presented in the Table below. 4 patients were re-administered anti-PD-1 in the 2L after PD and local treatment for PD. mPFS was higher in the Pem/Len group but no statistically significant differences (SSD) were observed between all groups for either PFS, OS1 or OS2. Among pts in the Ipi/nivo group nearly half progressed on anti-PD-1 at the first CT/MRI assessment (see the Table). Only 6,2% had an objective response to anti-PD-1 earlier (CR+PR). Generally, the PD group had the lowest survival rates (the exception of the PR group of 2 pts), although no SSD were found between groups in PFS, OS1, and OS2. Conclusions: Ipi/nivo remains the primary 2L option for BRAFwt aM. No SSD between subgroups were found. The highest PFS in the Pem/Len may be attributed to the mechanism of action of this combination. Previous responses to anti-PD-1 in 1L may influence the effect of Ipi/nivo. These results need to be interpreted with caution given its retrospective nature and small number of pts in groups. Total n=86 (100%) Ipi/nivon=65 (75,6%) CTX10 (11,6%) Pem/Len5 (5,8%) Anti-PD-14 (4,7%) Trame (NRAS+)2 (2,3%) mPFS, mo 3,5 (3,0 - 6,2) 2,63 (2,3 - Na) 11,7 (3,6 - Na) 4,65 (3,5 - Na) 1,15 (1,0 - Na) mOS2, mo 21,8 (17,5 - 34,3) 8,8 (4,7 - Na) 11,5 (Na - Na) 13,7 (10,9 - Na) 1,3 (Na - Na) mOS1, mo 36,2 (28,1 - 55,4) 13,8 (12,3 - Na) Na 58,4 (21,8 - Na) Na (21,9 - Na) Survival in Ipi/nivo (n=65) Best response on anti-PD-1 in 1L CR2 (3,1%) PR2 (3,1%) SD20 (30,8%) PD32 (49,2%) Unk9 (13,8%) mPFS, mo 3,8 (3,8 - Na) 5,9 (5,8 - Na) 5,1 (2,8 - 10,2) 3,0 (2,6 - 6,2) 3,9 (2,8 - Na) mOS2, mo 34,3 (34,3 - Na) 6,7 (6,7 - Na) 32,1 (17,9 - Na) 18,2 (13,43 - 31,6) 39,1 (9,8 - Na) mOS1, mo 65,9 (65,9 - Na) 23,4 (23,4 - Na) 48,1 (30,8 - Na) 24,6 (20,9 - 36,9) 55,4 (31,8 - Na)
Impact of diabetes and glycemic control on pathologic complete response after neoadjuvant chemotherapy in breast cancer in an Afro-Caribbean population: A retrospective cohort study.
e12625 Background: Diabetes mellitus and hyperglycemia may adversely affect cancer outcomes and response to systemic therapy in breast cancer (Peairs et al., 2010; Srokowski et al., 2009). Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a validated surrogate marker of improved long-term outcomes (Spring et al., 2020; van Mackelenbergh et al., 2023). This study evaluated whether diabetes and baseline HbA1c are associated with pCR in breast cancer patients receiving NACT. Methods: We conducted a retrospective cohort study of breast cancer patients treated with NACT at a single institution. Included patients had a documented neoadjuvant chemotherapy regimen, known pCR status, and known diabetes status, defined as HbA1c ≥ 6.5. The primary outcome was pCR (yes/no). The main exposures were diabetes (yes/no) and HbA1c at diagnosis. Categorical variables were compared using Fisher’s exact test, and continuous variables using Welch’s t-test; multivariable logistic regression was used to estimate adjusted odds ratios (ORs) for pCR, including diabetes, age, BMI, and HbA1c. Results: Of 153 patients who received NACT, 52 had complete data for diabetes and pCR and were included in the primary analysis. Among these, 40 (76.9%) had diabetes and 12 (23.1%) did not have diabetes; 30 (57.7%) achieved pCR. pCR occurred in 75.0% of patients without diabetes versus 52.5% of patients with diabetes (Fisher’s exact OR = 0.37; p = .20). Baseline HbA1c was higher in patients without pCR than in those with pCR (mean 8.05% vs. 7.19%; p = .22). In multivariable logistic regression, diabetes was not an independent predictor of pCR (adjusted OR = 0.33; 95% CI [0.03, 4.31]). Age, BMI, and HbA1c were also not significantly associated with pCR. Conclusions: In this cohort, diabetes status and baseline HbA1c were not significantly associated with pCR after NACT, although both diabetes and higher HbA1c showed non-significant trends toward lower pCR rates. Larger, adequately powered studies are needed to clarify the impact of diabetes and glycemic control on neoadjuvant treatment response in breast cancer.