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Impact of remote symptom monitoring on acute care utilization in phase I cancer patients: Secondary analysis of a randomized clinical trial.
1505 Background: Patients with advanced cancer undergoing Phase I therapies often experience high symptom burden and complications, which may result in acute care encounters (i.e., emergency department [ED] visits and hospitalizations). Few studies have characterized these acute care encounters in Phase I patients. Furthermore, it is unclear if these encounters were avoidable and whether remote symptom monitoring (RSM) could reduce acute care utilization. We performed a secondary analysis of a randomized clinical trial to assess the impact of RSM on ED visits and hospitalizations in Phase I patients. Methods: This is a secondary analysis of a randomized clinical trial comparing specialist palliative care (SPC) alone and SPC+RSM in patients with advanced cancer enrolled in Phase I trials at MD Anderson Cancer Center. The key outcomes were the frequency of ED visits and hospitalizations over 6 months following enrollment. We documented the main presenting symptoms and reasons for acute care encounters. Additionally, two independent reviewers assessed whether these encounters were potentially avoidable, defined as whether timely outpatient involvement (e.g., nursing telephone call, clinic visit) could have prevented the encounter. We compared the outcomes between the two study groups using Fisher’s exact test. Results: Among 100 enrolled patients (mean age 64, 63% female, 33% gastrointestinal cancers, median survival 221 [95% CI 171, 271] days), 43 were in the SPC group and 57 were in the SPC+RSM group. 22/43 (51%) SPC patients and 30/57 (53%) SPC+RSM patients had at least one ED visit over 6 m (P=0.61, Table). 15/43 (35%) SPC patients and 21/57 (37%) had at least one hospitalization over 6 m (P=0.63, Table). Only 4/84 (5%) ED visits and 0/100 (0%) of the admissions were deemed avoidable. The most common presenting symptoms were pain (ED 27%, hospitalizations 30%) and respiratory distress (ED 23%, hospitalization 23%). The main reasons for acute care encounters were disease progression (ED 49%, hospitalizations 58%), acute complications (ED 26%, hospitalizations 28%) and treatment-related complications (ED 13%, admissions 11%). Conclusions: Phase I patients had high rates of ED visits and hospitalizations even when they were followed by SPC. The addition of RSM did not reduce the rates of these encounters. A vast majority of these visits were deemed unavoidable, attributed to disease progression and acute complications. These findings underscore the need for novel interventions to support Phase I patients as they navigate the acute care system near the end of life. Clinical trial information: NCT04989556 . Frequency of acute care utilization over 6 months in phase I patients. ED Visits ED Visits Hospitalizations Hospitalizations # of visits SPC n=43 (%) SPC+RSM n=57 (%) SPC n=43 (%) SPC+RSM n=57 (%) 0 21 (49) 27 (47) 25 (58) 36 (63) 1 16 (37) 16 (28) 14 (33) 12 (21) 2 4 (9) 8 (14) 3 (7) 7 (12) 3 1 (2) 5 (9) 1 (2) 1 (2) 4 0 0 0 0 5 1 (2) 1 (2) 0 1 (2)
MSNPseq: An NGS-based assay for chimerism detection and risk assessment in allogeneic HSCT.
6557 Background: Chimerism (CHIM) analysis assesses the ratio of donor to recipient hematopoietic cells, confirming engraftment and detecting impending graft failure or relapse, in allogeneic hematopoietic stem cell transplantation (aHSCT). However, the conventional short tandem repeat (STR) analysis, has limited sensitivity (1–5%), often missing low-level CHIM. In this retrospective study, Multiple Single Nucleotide Polymorphism sequencing (MSNPseq), an NGS-based assay targeting DNA fragments each harboring 4–8 SNPs, demonstrated superior sensitivity and specificity compared with STR analysis, enabling reclassification of STR-negative cases and improved prognostic stratification. Methods: MSNPseq, based on Ion AmpliSeq technology, amplifies 100 fragments for sequencing on the Ion Torrent PGM platform, achieving >2000× depth for 96.8% of loci. Its sensitivity and accuracy were validated in simulated chimeric and post-transplant samples against STR analysis. Calibration models used pre-transplant donor/recipient data to generate tailored correction coefficients. CHIM was assessed via MSNPseq at three 30-day time points (TP1, 2, 3) post-transplant, in 741 aHSCT patients (AML 49.9%, ALL 27.4%, MDS 13.5%, lymphoma 4.7%, others 4.5%). PFS and OS were stratified by CHIM status and its dynamics to evaluate transplant outcomes, prognostic significance, and late relapse. Results: CHIM sensitivity was assessed using BCR-ABL1–positive standards. MSNPseq achieved a 0.01% detection limit, outperforming STR (1%) with strong correlation (R² = 0.9953). CHIM status was classified by donor fraction as complete (cCHIM, 100%), microchimerism (mCHIM, 99% to <100%), subthreshold chimerism (sCHIM, 95% to <100%; below STR sensitivity), and incomplete chimerism (iCHIM, ≤95%) across three time points. While iCHIM was consistently associated with inferior PFS and OS, sCHIM and mCHIM also showed worse outcomes compared with cCHIM, defining distinct high-risk subsets. CHIM dynamics revealed decreasing sCHIM/mCHIM and increasing cCHIM/iCHIM over time. Notably, a sustained CHIM decrease >0.5% over two consecutive time points was associated with significantly poorer OS and PFS. Interestingly, sCHIM and mCHIM status, as well as a sustained CHIM decrease >0.5% over two consecutive time points, were also associated with a high risk of acute graft-versus-host disease (aGvHD). Overall, MSNPseq enables more precise CHIM stratification than STR, improving post-transplant risk assessment. Conclusions: MSNPseq's superior sensitivity enables more precise chimerism classification and detection of clinically relevant sCHIM and mCHIM subsets that STR often misses. These refined CHIM categories, along with sustained CHIM decline, correlate with poorer survival and higher aGvHD risk, supporting MSNPseq as a superior tool for post-aHSCT risk stratification and therapeutic guidance.
HER2-positive central nervous system (CNS) surveillance: A study of the feasibility of randomizing women and men with HER2-positive metastatic breast cancer to CNS surveillance versus no surveillance.
TPS1146 Background: Breast cancer (BC) is the second most common primary tumour to metastasise to the brain (Aragon-Ching, 2017). Clinical data have demonstrated that BC brain metastases (BCBM) are an increasing clinical problem (Akshara, 2024). Improved systemic treatment of extracranial disease has prolonged survival (DESTINY-Breast9, 2025); coupled with more CNS imaging, this likely contributes to rising BCBM incidence (Frisk, 2012; Pedrosa, 2018). HER2+ BC has a predilection for the CNS (Sun, 2022), and real-world data from the ESMÉ programme report BCBM incidence in metastatic BC (MBC) (Darlix, 2019). Cumulative incidence at 12 months after MBC diagnosis in a cohort of 16,703 MBC pts was 16.8% and 32.4% for HER2+ /HR+ and HER2+ /HR- respectively; at 24 months, 29.2% and 49.0%, respectively. Given the high risk of CNS disease in HER2+ MBC, associated morbidity/mortality (Riecke, 2023) and the evidence that there may be a survival and quality of life advantage for early asymptomatic detection (Hurvitz, 2019; Laakmann, 2020), surveillance strategies for early detection need evaluation. Methods: This is a multi-centre, randomised study in pts with HER2+ MBC without prior CNS disease. The study is testing the feasibility of randomising pts to CNS screening vs none. The study is recruiting male/female pts, aged ≥16 years with HER2+ BC with visceral metastases who are currently on HER2 directed therapies. It excludes pts with a history/clinical symptoms of CNS disease, unable to undergo MRI, or with bone only MBC. Pts following a baseline MRI brain, to exclude occult disease, are randomised 1:1 to 6 monthly MRI brain with contrast for a year or no CNS imaging. Primary endpoint: feasibility of randomising HER2+ MBC pts with no CNS disease to surveillance vs no surveillance. Secondary endpoints: proportion of pts with occult CNS disease at baseline, proportion developing occult CNS disease during surveillance and proportion developing symptomatic CNS disease during the study. The management of detected CNS disease on study will be documented. Further qualitative research through a series of interviews/focus group discussions will explore reasons why pts either agree/refuse randomization, to identify challenges with study implementation and delivery. Statistics: A maximum of 193 pts are to be approached; with 69 pts agreeing to be consented to the study for a larger study to be deemed feasible (based on alpha=5% and power 90%). Recruitment will halt at 69 consented/193 approached, whichever is reached first. REC/IRAS project ID: 341272.
SARS-CoV-2–associated Epstein–Barr virus reactivation and lymphomagenesis: A systematic review and meta-analysis.
e22586 Background: SARS-CoV-2 infection induces marked immune dysregulation, a biologic milieu permissive for reactivation of latent oncogenic viruses. Epstein–Barr virus (EBV) reactivation is a recognized precursor to B-cell lymphoproliferative disease in immunocompromised states. We conducted a systematic review and meta-analysis of EBV reactivation following SARS-CoV-2 infection and contextualized these findings within epidemiologic evidence relevant to lymphoma risk. Methods: Studies evaluating EBV reactivation after SARS-CoV-2 infection were identified through systematic review. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed using Cochran’s Q and I² statistics. Population-based cohorts, ecological analyses, and case reports examining lymphoma occurrence in the setting of COVID-19 were reviewed qualitatively. Results: Three studies met inclusion criteria for quantitative synthesis (n = 480). Meta-analysis demonstrated a significantly increased risk of EBV reactivation among SARS-CoV-2–infected patients (pooled RR = 3.69, 95% CI 2.56–5.32), with no significant heterogeneity (Q = 1.82, I² = 0%). Population-level data further support a non-random association between COVID-19 and lymphoma. A large cohort study of hospitalized cancer patients demonstrated substantially higher odds of COVID-19 diagnosis among patients with lymphoma compared with colon cancer controls (adjusted OR 11.13). An ecological analysis identified geographic correlation between historical non-Hodgkin lymphoma incidence and COVID-19 burden. Case reports describe EBV-driven B-cell lymphoproliferative disorders emerging shortly after SARS-CoV-2 infection, though data remain insufficient for quantitative lymphoma incidence estimation. Conclusions: SARS-CoV-2 infection is associated with a nearly four-fold increased risk of EBV reactivation across available cohorts. Integrated with epidemiologic observations, these findings support biologic plausibility for COVID-19–associated immune dysregulation contributing to EBV-mediated lymphomagenesis. Establishing causality will require prospective longitudinal studies incorporating standardized viral surveillance, immune profiling, and rigorous control of confounding factors. These results underscore the importance of infectious disease control, post-infectious monitoring, and risk stratification at the interface of oncology and viral immunity. Summary of studies evaluating EBV reactivation following SARS-CoV-2 infection. Study Population EBV Reactivation Rate (COVID-19) EBV Reactivation Rate (Controls) Paolucci et al., 2021 Hospitalized adults ~50% ~10% Bernal & Whitehurst, 2023 Hospitalized adults 37.5% 10% Bernal & Whitehurst, 2023 Mixed inpatient/outpatient 33.3% 12%
Association of protein-energy malnutrition with mortality, resource utilization, and discharge disposition in pancreatic cancer: An analysis of the National Inpatient Sample (NIS).
e16364 Background: Pancreatic cancer is associated with substantial morbidity and mortality, with an overall 5-year survival relative survival of 12%. Protein-energy malnutrition (PEM) is a frequent complication of pancreatic cancer, and may worsen clinical outcomes. PEM has been linked to worse tolerance of oncologic therapies and increased morbidity, however its impact on in-hospital outcomes and discharge remains poorly defined at a national level. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (2016-2022). Adult hospitalizations with pancreatic cancer and PEM were identified using appropriate ICD-10-CM codes. Multivariable regression models were used to calculate adjusted odds ratios (aOR), identify predictors of PEM, and assess the impact of PEM on in-hospital mortality, hospital length of stay (LOS), discharge disposition, and total hospital charges among patients with pancreatic cancer. Results: Among 263,890 hospitalizations for pancreatic cancer, 71,475 (27.1%) had coexisting PEM Compared to patients without PEM, those with PEM had higher in-hospital mortality (7.9% vs 5.9%, p < 0.001), longer LOS (9.3 vs 6.1 days, p < 0.001) and higher total hospital charges ($116,316 vs $86,486, p < 0.001). After adjustment, PEM was found to be an independent predictor of increased in-hospital mortality (aOR 1.52, 95% CI 1.41-1.64) and discharge to a skilled nursing facility (aOR 1.94, 95% CI 1.82–2.07). PEM was associated with 45% longer LOS (adjusted incidence rate ratio 1.45, 95% CI 1.41-1.49) and 31% higher hospital charges (Exp[β] 1.31, 95% CI 1.27 – 1.35). Conclusions: PEM is common among hospitalized patients with pancreatic cancer and is independently associated with higher in-hospital mortality, prolonged hospitalization, greater healthcare utilization, and non-routine discharge. These findings highlight PEM as a major, potentially modifiable risk factor and support routine nutritional screening and early intervention as strategies to improve outcomes in this high-risk population. In-hospital outcomes and discharge disposition of patients with pancreatic cancer with and without protein-malnutrition. In-Hospital Outcomes and Discharge Disposition Without PEM(n = 192, 415) With PEM(n=71,475) P-Value Mortality, n (%) 10,040 (5.2) 5,665 (7.9) <0.001 Length of stay, mean (SD), days 6.1 ± 6.8 9.3 ± 9.4 <0.001 Total Charges, mean (SD), $ 86,486 ± 98,521 116 ± 142,876 < 0.001 Home (self-care) 110,285 (57.4) 26,950 (37.7) < 0.001 Short-term hospital 4,620 (2.4) 1,375 (1.9) <0.001 Skilled nursing facility 19,690 (10.2) 12,880 (18.0) <0.001 Home health care 46,475 (24.2) 24,270 (34.0) <0.001 AMA/Died 11,030 (5.7) 5,960 (8.3) <0.001 Abbreviations: PEM, protein-energy malnutrition; SD, standard deviation; AMA, against medical advice.
Disentangling <i>KEAP1</i> and <i>STK11</i> in <i>KRAS</i> -mutant ( <i>KRAS</i> m) non–small cell lung cancer (NSCLC) treated with immunotherapy.
e20583 Background: KEAP1 and STK11 are associated with poor response to immune checkpoint inhibitors (ICIs) in KRAS m NSCLC, but their distinct vs. combined effects are incompletely defined. Methods: We analyzed metastatic KRAS m NSCLC patients treated with ICIs at multiple centers, with external validation in the US-based deidentified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic Database. PFS/OS and real-world time-to-next-treatment (rwTTNT)/rwOS were the primary outcomes in the academic and Flatiron cohorts, respectively. Patients were stratified as KEAP1 m only (K), STK11 m only (S), co-mutant (KS), or wildtype (WT). To identify their predictive effects independent of other clinicogenomic variables, XGBoost models were trained to predict PFS > 6 months from anti-PD-1 monotherapy (ICI-mono) or chemo-immunotherapy (ICI-chemo). SHAP identified feature importance. The academic cohort was split 80/20 into train/test and Flatiron served as external validation. CD8⁺ T-cell infiltration was assessed by immunofluorescence and validated using MCP-counter-inferred CD8⁺ T-cells from TCGA. Results: The academic and flatiron cohorts included 1019 and 2261 patients, respectively. As compared to WT tumors treated with ICI-mono (n=387), K tumors had no difference in PFS (n=58, HR 1.2, p=0.25), while S (n=56; HR 1.9, p<0.001) and KS tumors (n=75; HR 2.2, p<0.001) had progressively worse PFS. OS mirrored this: K tumors had no difference (HR 1.3, p=0.13); S (HR 1.6, p=0.0032) and KS tumors had progressively worse OS (HR 2.4, p<0.001). As compared to WT tumors treated with ICI-chemo (n=219), K tumors trended toward worse PFS (n=35; HR 1.4, p=0.10), while S (n=60; HR 1.4, p=0.033) and KS tumors (n=89; HR 2.2, p<0.001) had progressively worse PFS. OS was similar for S tumors (HR 1.2, p=0.38) but worse for K (HR 1.8, p<0.001) and KS tumors (HR 1.9, p<0.001). Flatiron validation confirmed these results. As compared to WT tumors (median PD-L1 30%), PD-L1 was lower in K (5%), and even lower in S (0%) and KS (0%) tumors. XGBoost models performed well for ICI-mono (test: AUC=0.70; Flatiron: rwTTNT HR 0.6, p<0.001) and ICI-chemo (test: AUC=0.73; Flatiron: HR 0.6, p<0.001). KS was the most predictive genomic feature in each model; K or S were not predictive. Compared with WT tumors, overall CD8 T-cell density was reduced in K and KS, but not S, tumors, a finding validated in TCGA. In contrast, CD8 T-cell density was reduced in the tumor-compartment in S and KS, but not K, tumors, suggesting that KEAP1 impairs global CD8 infiltration, whereas STK11 restricts intratumoral CD8 localization. Conclusions: In KRAS m NSCLC, KEAP1 and STK11 exhibit varying predictive and prognostic effects and immune-phenotypes depending on whether they occur alone or together. These findings have implications for risk stratification, treatment selection, and the development of therapeutics to overcome ICI resistance in these patients.
Psychological burden and burnout among regional healthcare providers communicating hereditary tumor findings: A multi-institutional communication skills training implementation study.
9020 Background: Psychological burden among healthcare providers in precision oncology affects workforce sustainability. In regional settings with limited genetic counseling resources, providers face compounded stress disclosing hereditary tumor findings to cancer patients. This implementation study, supported by an MSD Medical Education Grant for advancing genetic medicine understanding in biomarker-based precision oncology, assessed structured communication skills training to address provider psychological burden. Methods: We deployed a standardized curriculum across seven regional hospitals in Yamagata Prefecture, Japan, in 2025, integrating SHARE protocol training (Fujimori et al., JCO. 2014) with modules on BRCA testing, microsatellite instability, and genomic profiling disclosure. Implementation strategies included professional actors experienced in medical scenarios, facilitated role-playing, and videotaped quality monitoring. This single-arm pre-post intervention study used a mixed-methods evaluation with questionnaire surveys and qualitative inquiries with a modified grounded theory through an inductive thematic analysis until theoretical saturation. Results: Among 263 participants (median experience 10 years, range 0-36), including physicians, nurses, genetic counselors, pharmacists, and administrative staff, 93% had baseline psychological burden and 92% reported anxiety when communicating hereditary tumor findings. Psychological burden and anxiety post-intervention decreased in 89% (p<0.001) and 84% (p<0.001), respectively, with 89% reporting an improved hereditary tumor understanding (p<0.001). A qualitative analysis of 18 semi-structured interviews revealed five critical themes: persistent institutional barriers to genetic counseling in resource-limited regions, profound emotional exhaustion from simultaneously managing terminal illness and germline implications, role-play enabling authentic skill rehearsal without patient risk, moral distress balancing patient autonomy against family cascade obligations in limited-prognosis contexts, and the critical need for sustained peer support. Conclusions: Multi-site communication skills training including experiential role-play significantly reduced provider psychological burden and anxiety while improving hereditary tumor knowledge across diverse regional healthcare teams. A theory-driven mixed-methods evaluation strengthened intervention rigor. This study supports industry-academic partnerships addressing workforce sustainability while advancing genomic medicine equity in underserved settings. National dissemination with sustained outcome assessment will establish this model as a scalable framework addressing the global workforce crisis in precision oncology.
Multivariable analyses (MVAs) of overall survival (OS) in the phase 3 SUNMO, STARGLO, and POLARGO trials in relapsed/refractory large B-cell lymphoma (LBCL).
7093 Background: Phase 3 trials, notably SUNMO (NCT05171647), STARGLO (NCT04408638) and POLARGO (NCT04182204), have shown superior efficacy of combination treatments over rituximab (R) + gemcitabine and oxaliplatin (GemOx) in second line or later LBCL. However, baseline imbalances may impact the robustness of efficacy results, even with stratified randomization. We conducted MVAs of SUNMO, STARGLO and POLARGO to assess OS. As the target number of OS events was not reached at the SUNMO interim OS analysis, to increase the sample size we also conducted a pooled analysis of mosunetuzumab (Mosun) + polatuzumab vedotin (Pola; data from SUNMO and GO40516 [Phase 2; NCT03671018]) vs R-GemOx (comparators from SUNMO, STARGLO and POLARGO). Methods: A multivariable Cox regression model was used to estimate treatment effect while adjusting for potential confounding factors selected by a systematic process involving: 1) univariable analysis of prespecified baseline factors; 2) multicollinearity assessment of pairwise correlation among selected factors; 3) MVA of the experimental arm (SUNMO: Mosun-Pola; STARGLO: glofitamab [Glofit]-GemOx; POLARGO: Pola-R-GemOx) vs the control arm (R-GemOx) and selected non-collinear prognostic baseline factors from steps 1 and 2. Results: In SUNMO, patients treated with Mosun-Pola had more high-risk features, such as a higher ECOG performance status and greater bulky disease, vs those treated with R-GemOx. The MVA-adjusted hazard ratio (HR, 0.65 [95% confidence interval [CI]: 0.41–1.02]) was more favorable than the unadjusted interim OS HR (0.80 [95% CI: 0.54–1.20]) for Mosun-Pola vs R-GemOx. The MVA-adjusted HR for POLARGO was also more favorable than the unadjusted HR; the HR for STARGLO remained largely unchanged (Table). A pooled MVA was used to increase the sample size, noting baseline differences between trials (e.g. ≥2 prior lines of therapy: SUNMO, 56%; STARGLO, 37%; POLARGO, 35%). In this pooled analysis, OS HRs favored Mosun-Pola vs R-GemOx in the unadjusted (HR, 0.62 [95% CI: 0.48–0.81]) and MVA-adjusted (HR, 0.59 [95% CI: 0.44–0.81]) models, with lower HRs and narrower 95% CIs vs the MVA of SUNMO alone. Conclusions: The MVAs support favorable OS benefits in SUNMO, STARGLO and POLARGO, all with an MVA-adjusted OS HR ≤0.65 vs R-GemOx. The pooled MVA further supports the OS benefit of Mosun-Pola vs R-GemOx. Overall, the MVAs show that baseline imbalances can influence OS estimates, thus multivariable adjustment is important when interpreting pooled or cross-trial comparisons. Clinical trial information: NCT05171647 , NCT04408638 , NCT04182204 , NCT03671018 . SUNMO n=208 STARGLO n=274 POLARGO n=255 Pooled Mosun-Pola vs R-GemOx n=465 Median follow-up, months (range) 23.2 (0–32) 20.7 (0–36) 24.6 (0–34) – MVA-adjusted OS HR (95% CI) 0.65 (0.41–1.02) 0.63 (0.44–0.90) 0.52 (0.36–0.74) 0.59 (0.44–0.81) Unadjusted OS HR (95% CI) 0.80 (0.54–1.20) 0.62 (0.43–0.88) 0.60 (0.43–0.83) 0.62 (0.48–0.81)
Non-D842V platelet-derived growth factor alpha (PDGFRA) mutant gastrointestinal stromal tumours (GISTs): A distinctive and heterogeneous subgroup— Experience from regional centre in United Kingdom.
e23517 Background: PDGFRA GISTs account for 10-15% of all gists and are almost exclusively gastric in origin. Around 50% of PDGFRA gists have mutations other than exon 18 D842V mutation. These Non D842V PDGFRA mutant gists are ultra rare and the natural history and response to kinase inhibitors is not well known. We present our 15 year experience with PDGFRA Non D842V gist from a regional centre in United Kingdom. Methods: Data from the Cambridge GIST database was analysed from 2010-2015. Non D842V gist patients demographics, tumour characteristics, mutational status and response to tyrosine kinase inhibitors (TKIs) was extracted. Response to TKIs was evaluated on imaging and/or histology. Results: N = 40. M:F 26:14, Median age 64 years (range 15-84). Primary site of gist was gastric in 39 and 1 patient had extra gastrointestinal gist (E-GIST). Anatomical location ins stomach--22/40 in prepyloric/antral/distal body and 18/40 in midbody/lesser curve/greater curve. No PDGFRA gists were noted in gastric cardia or fundus Median size 7 cm (range 1-30 cm). Histology--31/40 were epithelioid or mixed only 9/40 had spindle cell morphology. Mitotic index median 4, range 0-50. On immunohistochemistry, 17/40 had patchy CD117 staining and 6/40 had patchy desmin positivity. All gists were DOG-1 positive. Treatment outcomes: 3 patients treated with Imatinib in neoadjuvant/metastatic setting had radiological and or histological responses. 3 patients were treated with 4th line Sorafenib (PDGFRA exon 18 codon 843-847 deletion). Subjective improvement was observed in all three patients and one patient has ongoing partial response. Dose reduction was needed all three patients. Conclusions: PDGFRA Non D842V gists are a heterogenous and distinct subgroup of gists. These are sensitve to imatinib. Sorafenib is active in gists with PDGFRA exon 18 codon 843-847 deletion. Larger datasets are needed to characterise the natural history, TKI responsiveness and resistance mechanisms in PDGFRA non D842V gists. Distribution & types of PDGFRA mutations. Number of patients PDGFRA Exon Mutation Comments 11 12 Codon 561 (p.Val561Asp) Most common exon 12 mutation (50%) 5 14 Codon 659 (p.Arg659Tyr) Hot spot mutation 100% 24 18 Codon 842-847 del/ins or deletion 80%
<i>ESR1</i> mutation longitudinal dynamics in RWD cohort of HR+/HER2− metastatic breast cancer patients treated with standard-of-care hormonal therapy.
3062 Background: ESR1 mutations ( ESR1 m) are known drivers of resistance to aromatase inhibitors. While ESR1 m has been linked to worse survival outcomes, clonal complexity over time has not been well-evaluated in a real-world context. Here we characterized longitudinal dynamics of ESR1 m, including rare point mutation emergence and polyclonality in hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC) patients (pts) treated with aromatase inhibitor (AI) plus CDK4/6 inhibitor (CDK4/6i). Methods: We identified a cohort for longitudinal analysis from the Tempus real-world database (RWD). Eligible pts had HR+/HER2- mBC (diagnosed before 01/2023), received AI+CDK4/6i therapy in mBC, and had comprehensive genomic profiling from tissue/liquid biopsy (Tempus xT/Tempus xF) within 2 yrs of treatment, with ≥1 on-treatment xF tests. We analyzed ESR1 clonal dynamics, starting from first ESR1 m detection in a subset of pts who had multiple xF tests. Polyclonality was also assessed, defined as presence of at least 2 distinct ESR1 m in a sample. Results: Of 301 HR+/HER2- mBC pts on AI+CDK4/6i therapy, 102 (33.9%) developed an ESR1 m. In the ESR1 m group, 72 pts (70.6%) had 2+ on-treatment liquid biopsies (Tempus xF/xF+), comprising the final cohort for observation. At ESR1 m detection, 64.8% pts had a single detectable ESR1 m, most commonly D538G (31.9%) and Y537S (12.5%). In contrast, 34.7% had polyclonal mutations (19.7% with 2 distinct mutations; 15.3% with 3+). Recurrent detection of D538G (52.8%), Y537S (20.8%), and Y537N (16.7%) was noted in repeat xF testing. Detection of additional ESR1 m (26.4%) over time confirmed known common mutations such as Y537N (8.3%), D538G (5.6%), and Y537S (5.6%). However, longitudinal testing also found rare mutations such as V422del and H524L. Mutational dynamics shifts were also revealed by longitudinal testing. In 36.1% pts, a previously detected ESR1 m was no longer found, often in those who initiated a SERD. D538G (5.6%) and Y537N (4.2%) were the most commonly lost mutations. Recurrent and new ESR1 m detection occurred in pts who continued AI+CDK4/6i (44.4%). Many pts showed a combination of these dynamics. Conclusions: Multimodal RWD analyses demonstrate valuable clinical insights on ESR1 m patterns detected from longitudinal molecular surveillance testing in HR+/HER2- mBC pts treated with AI+CDK4/6i. We observed shifting dynamics in ESR1 m burden, including detection of rare mutations and polyclonality. These findings show the value of monitoring ESR1 m longitudinally over disease course and prompt further research into clinical impacts of clonal dynamics.
A phase 1/2 study of TSN1611, a highly selective oral KRAS G12D inhibitor, in solid tumors: Efficacy and safety in <i>KRAS</i> G12D–mutated NSCLC patients.
8516 Background: There remains an unmet clinical need for effective therapies targeting KRAS G12D mutation in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to prior treatments. TSN1611 is a novel oral small-molecule inhibitor designed to bind both the active GTP-bound (ON) and inactive GDP-bound (OFF) conformations of KRAS G12D, providing a differentiated mechanism of action and broad antitumor activity in preclinical models. Methods: This multi-regional Phase 1/2 study enrolled pts with advanced solid tumors harboring KRAS G12D mutation. Phase 1a dose-escalation part evaluated TSN1611 at 50–1200 mg twice daily (BID). A subsequent Phase 1b dose-optimization part evaluated 800 mg and 1200 mg BID. In Phase 2, efficacy is being further explored across multiple tumor types at the recommended Phase 2 dose of 1200 mg BID. Results: As of Jan 23, 2026, 117 pts received TSN1611 across all dose levels in Phase 1/2. Tumor types included NSCLC (n = 26), pancreatic adenocarcinoma (n = 50), colorectal cancer (n = 35), and others (n = 6). Median age was 62 yrs (range 22-81). The median prior lines of systemic therapy were 2 (range 0-7). The most common (≥10%) treatment-related adverse events (TRAEs) in all treated pts were diarrhea (53.0%), nausea (48.7%), vomiting (46.2%), anemia (17.9%), decreased white blood cell count (16.2%), decreased neutrophil count (13.7%), increased ALT (12.8%), decreased appetite (12.0%), decreased platelets (11.1%), fatigue and increased AST (10.3% each). Grade 3 TRAEs occurred in 9.4% of pts; these were all single events (0.9% each) except for anemia, diarrhea, and asymptomatic lipase elevation, which occurred in 1.7% of pts each. TRAEs led to dose interruption in 17.1% pts and dose reduction in 7.7% pts; no treatment discontinuations due to TRAEs occurred. Among 26 NSCLC pts, all had stage IV metastatic disease; 22 (84.6%) had received prior chemotherapy and/or PD-1/PD-L1 inhibitors, and 9 (34.6%) had received prior anti-angiogenic therapy. Among 20 response-evaluable NSCLC pts treated with TSN1611 at 600–1200 mg BID, 10 achieved partial response, 8 had stable disease, and 2 had progressive disease, yielding an objective response rate (ORR) of 50% (95% CI 27.2–72.8) and a disease control rate (DCR) of 90% (95% CI 68.8–98.3). Median time to response was 1.4 months (range 1.2–3.5). In addition to extracranial responses, rapid intracranial responses were observed. Median progression-free survival (PFS) was not mature yet (range 1.3+ to 12.9+ months), with a 9-month PFS rate of 54.5% (95% CI 24.4–77.0). Enrollment continues and updated data will be presented at the conference. Conclusions: TSN1611 demonstrated a favorable safety profile and clinically meaningful antitumor activity in pts with KRAS G12D mutated NSCLC. Further development of TSN1611 as monotherapy and in combination regimens is ongoing. Clinical trial information: NCT06385925 .
Biomarker landscape and survival outcomes in gastric adenocarcinoma: A Hispanic/Latino cohort from Colombia (2010–2024).
e16088 Background: Hispanic patients with gastric adenocarcinoma show distinct clinical patterns, including earlier onset, increased mortality, and a distinct molecular profile. Despite recognition that ethnicity shapes tumor biology and precision oncology access, Latin American real-world data on this disease remain scarce. Methods: We conducted a retrospective observational cohort study of adults diagnosed with gastric adenocarcinoma treated at Fundación Santa Fe de Bogotá between 2010 and 2024. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier (KM) method. Survival curves were compared using the log-rank test, and Cox proportional hazards regression models were performed to identify factors associated with OS and PFS. Results: A total of 166 patients were included; 51.8% were female, with a median age of 66 years (IQR 25). Stage IV disease was frequent (37.6%), predominantly involving the peritoneum (70.4%). Notably, 18.1% of patients were asymptomatic at diagnosis. Diffuse-type histology was most common (47.6%), and 60.6% of tumors were grade III. HER2 overexpression (IHC 3+) and MSI-high status were observed in 6.1% and 6.8%, respectively. Biomarker testing was available in a subset of patients: MSI status was assessed in 79 patients, with 13.9% classified as MSI-high, and HER2 status was evaluated in 106 patients, of whom 13.2% were HER2-positive. Systemic therapy was administered to 82.9% of patients, with chemotherapy as the backbone of treatment (97.0%), the most commonly used regimens were FOLFOX (25.9%) and FLOT (22.3%), followed by CAPEOX (6.0%) and DCF (3.6%). After a median follow-up of 41.0 months using the reverse KM method, median OS and PFS were not reached. Twelve- and 24-month OS rates were 77.6% (95% CI, 70.0–83.6) and 62.9% (95% CI, 54.2–70.4), respectively, while corresponding PFS rates were 58.4% and 41.0%. Disease stage was a strong predictor of both OS and PFS (p < 0.001 for both). OS differed according to MSI status, with MSI-high tumors associated with significantly improved survival (HR 0.13, 95% CI 0.02–0.90; p = 0.048). In contrast, HER2-positive status was not associated with OS (adjusted HR 0.71, 95% CI 0.25–2.00; p = 0.52). Conclusions: Diffuse histology and peritoneal metastasis were frequent in this Hispanic cohort, while HER2 overexpression and MSI-high status were uncommon, limiting targeted and immunotherapy-based approaches. Notably, MSI-high status was associated with significantly improved OS, indicating that the low prevalence of this subtype in our population may contribute to the overall poorer prognostic profile. Despite advanced-stage presentation, survival outcomes were comparable to international real-world series, highlighting the distinct biologic profile of gastric cancer in Hispanic populations and the need for greater representation in clinical research.
Whole-genome HRD phenotyping as a predictor of PARP inhibitor benefit in first-line maintenance high-grade serous ovarian cancer.
e17608 Background: Homologous recombination deficiency (HRD) in ovarian cancer identifies patients who may benefit from PARP inhibitor (PARPi) therapy beyond pathogenic germline or somatic BRCA1/2 mutations (g/s BRCA1/2 ). Despite increasing availability of whole-genome sequencing (WGS), the association between WGS-defined HRD (WGS-HRD) and PARPi maintenance outcomes in treated patients remains incompletely defined. Here, we evaluated PARPi outcomes in association with WGS-HRD and g/s BRCA1/2 profiling. Methods: We studied a prospective cohort of 84 patients with high-grade serous ovarian carcinoma. Each patient underwent matched tumor-normal WGS from FF (57%) or FFPE (43%) tissue and received PARPi maintenance as first-line (1LM) or second-line (2LM). Variant profiling and HRD phenotyping were performed by CancerVision (Inocras Inc.). Progression-free survival (PFS) was measured from PARPi start to clinical progression or censoring. Panel-based BRCA testing was available for comparison (n=50), and vendor scarHRD (n=35) was used to calibrate WGS-derived scarHRD. Results: Forty-seven patients (56%) received 1LM and 37 (44%) received 2LM. Median follow up was 46.6 months (range, 7.5-71.2) In the overall cohort, WGS-HRD(+) was associated with longer median PFS (mPFS) than WGS-HRD(-) (27.5 vs 12 months; HR=0.45, 95%CI 0.27-0.76; P<0.01). In 1LM, WGS-HRD(+) showed marked benefit (mPFS 44.2 vs 10.0 months; HR=0.36, 95%CI 0.16-0.76; P<0.01). In 2LM, PFS did not differ by WGS-HRD status (mPFS 17.4 vs 18.6 months; HR=0.68, 95%CI 0.32-1.44; P=0.31), suggesting attenuated predictiveness of baseline HRD phenotyping in later-line maintenance (potentially reflecting acquired resistance). WGS-based g/s BRCA1/2 calls were highly concordant with panel BRCA testing (accuracy 0.92, 95%CI 0.80-0.98; κ =0.83). g/sBRCA1/2 status alone was not significantly associated with PFS (mPFS 23.0 vs 20.2 months; HR=0.77, 95%CI 0.46-1.29; P=0.31); notably, 18/84 (21.4%) patients were BRCA-wildtype yet WGS-HRD(+), indicating that BRCA-only testing may not identify a clinically relevant subset of HRD-positive tumors. WGS-derived scarHRD was calibrated to third-party scarHRD calls, yielding a cutoff of 27 and moderate agreement (accuracy 0.74, 95%CI 0.57–0.88; κ =0.48). Unlike WGS-HRD, scarHRD was not significant in the overall cohort, but showed borderline stratification in 1LM (mPFS 33.8 vs 8.4 months; HR=0.45, 95%CI 0.18-1.15; P=0.09). In 2LM, scarHRD showed an opposite trend (HR=1.39, 95%CI 0.64-2.97; P=0.4), suggesting scarHRD is a less specific proxy for HRD than WGS-HRD. Conclusions: WGS-based HRD phenotyping stratifies PARPi maintenance benefit most strongly in the 1LM setting, with attenuated predictive value in 2LM. These findings support added clinical utility of WGS-HRD beyond BRCA-only testing to identify patients most likely to benefit from first-line PARPi maintenance.
Exploratory plasma ctDNA genomic biomarkers identified by whole-exome sequencing and a novel bioinformatics pipeline in advanced driver-negative NSCLC.
e20540 Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small-cell lung cancer (NSCLC), but predictive biomarkers remain suboptimal. Blood-based tumour mutational burden (bTMB) captures part of the signal, yet its clinical performance is inconsistent. Whole-exome sequencing (WES) of plasma-derived ctDNA, analysed through an automated, AI-enabled platform (AIRGenomics), may reveal broader genomic patterns associated with response or resistance to immunotherapy. Methods: We conducted a prospective observational study of 37 patients with advanced NSCLC without EGFR, ALK or ROS1 alterations treated in first line with pembrolizumab alone or chemo-immunotherapy. Baseline plasma ctDNA was analysed by WES and processed with the AIRGenomics platform (Nextflow-based pipeline for QC, alignment, somatic/germline calling, CNV and annotation) including an AI-based pathogenicity model. bTMB was calculated as somatic mutations/Mb. Unsupervised clustering was performed according to PD-L1 status and progression-free survival (PFS). Survival was assessed with Kaplan–Meier and Cox models. Results: Median bTMB was 12.31 mut/Mb. Higher bTMB was associated with tumours with PD-L1≥50% and adenocarcinomas but not with overall survival (OS) or PFS and showed limited discrimination for response (AUC 0.328). Cluster analysis by PD-L1/PFS identified recurrently altered genes (including KMT2C, CEP89 and TPSB2 ). Univariable survival analysis revealed 11 genes associated in mutated status with worse OS and PFS; among them, CYP4F2 (OS wild-type median not reached vs. mutated 9 months; p=0.011), ARSD (OS wild-type median not reached vs. mutated 13 months; p=0.017) and TPSB2 (OS wild-type 24 months vs. mutated 1,5 months; p=0.007) were selected for multivariable modelling. In the Cox model, CYP4F2 (HR=2,846; IC 95%: 1,102–7,352; p=0,031) and TPSB2 (HR=3,089; IC95%: 1,053–9,060; p=0,040) were independently biomarkers associated with shorter OS (χ² =13,128; p=0.004), and CYP4F2 (HR=3,167; IC95%: 1,384–7,244; p=0,006) remained an independent predictor of shorter PFS (χ² =11.116; p=0.011). Conclusions: This proof-of-concept study demonstrates that WES of ctDNA processed through the AIRGenomics platform is viable in real-world cases of advanced NSCLC treated with immunotherapy, detecting new potential candidate genes and pathways like predictive biomarkers, such as CYP4F2, ARSD , and TPSB2 . Multivariate Cox model of the CYP4F2, TPSB2, and ARSD genes. Gene HR (OS) IC95% (OS) p (OS) HR (PFS) IC95% (PFS) p (PFS) CYP4F2 2,846 1,102–7,352 0,031 3,167 1,384–7,244 0,006 TPSB2 3,089 1,053–9,060 0,040 2,073 0,693–6,201 0,192 ARSD 2,609 0,997–6,827 0,051 1,707 0,752–3,877 0,201
Immune priming with the EZH2 inhibitor tazemetostat in B-cell lymphomas receiving CAR T-cell therapy.
7035 Background: While chimeric antigen receptor (CAR) T cells have shown efficacy in B cell lymphomas, most patients (pts) still relapse. Preclinical studies have shown that inhibiting histone methyltransferase EZH2 prevents T cell exhaustion, promotes a T-cell memory phenotype, and sensitizes immune-based approaches. Methods: We administered the EZH2 inhibitor tazemetostat in pts receiving standard-of-care CART for diffuse large B cell, follicular, or mantle cell lymphoma (DLBCL, FL, MCL). Pts received tazemetostat for ≥7 days prior to apheresis and continued to lymphodepletion. Following CART, pts resumed tazemetostat at count recovery and continued for up to 12 mo (6 mo in pts with complete remission [CR]). Peripheral blood mononuclear cells were collected Day -24 and Day -5. To evaluate the immunomodulatory effects of priming, high parameter flow cytometry, RNA-seq with cell deconvolution, differential gene expression patterning, and functional gene signature scoring using ssGSEA were compared. Results: 13 pts enrolled (7 DLBCL, 5 FL, 1 MCL). Median prior lines of therapy were 2 (1-4), and 85% were refractory to the last therapy. EZH2 mutations were present in 2 pts. 4 pts had TP53 mutation or deletion, 4/7 DLBCL pts had MYC translocation and 3 had transformed disease. Five pts received axi-cel, 5 liso-cel, 2 tisa-cel, and 1 brexu-cel. All successfully completed CART manufacturing. The ORR was 100%, including 77% in CR (DLBCL 71%, FL 100%). At a median follow up of 18 months, 54% remain progression-free, and 77% remain alive. Ten pts (77%) experienced CRS, with 1 grade 3 CRS. 6 pts had transient grade 1-2 ICANS. Grade 3+ neutropenia was seen in 77%. Three pts experienced grade 3 infections. The most common AEs were gastrointestinal and almost exclusively grade 1-2. Comparing baseline and pre-CART samples, pts experienced a 14% and 20% increase in NK cells and CD16+ monocytes (p < 0.03) and a 14% and 53% decrease in Tregs and CD14+ monocytes (p < 0.02). Increases in the expression of functional gene signatures associated with MHC-I antigen presentation (p = 0.010), antigen-specific T cell activation (p = 0.019), and cellular cytotoxicity (p = 0.043) were also observed. Parallel reductions in signatures associated with tolerogenic dendritic cells (p = 0.011), myeloid suppression (p = 0.043), and coagulation (p = 0.030) were also seen. There was no observed negative impact on CART transduction efficiency, activation, or expansion. Conclusions: Addition of the EZH2 inhibitor tazemetostat is associated with high clinical efficacy and peripheral immune remodeling. Increases in lymphocyte activation and cytotoxicity along with decreases in myeloid tolerogenicity and immunosuppression could potentially augment CART expansion and persistence. Additional immune correlates are ongoing, and randomized studies are planned to validate this approach. Clinical trial information: NCT05934838 .
Sepsis severity and inpatient outcomes in metastatic cancer: A National Inpatient Sample study.
11197 Background: Sepsis is a major driver of acute decompensation and inpatient death in patients with cancer, with particularly poor outcomes reported among severe sepsis and septic shock. We evaluated national associations between sepsis severity and inpatient outcomes among metastatic cancer hospitalizations. Methods: We conducted a retrospective cross-sectional analysis of the National Inpatient Sample (2016–2020). Adult hospitalizations with metastatic cancer were identified using ICD-10-CM codes C77–C79. Sepsis severity was categorized as no sepsis, severe sepsis without shock, or septic shock using ICD-10 diagnosis codes. Survey-weighted multivariable logistic regression estimated adjusted odds ratios (aOR) for in-hospital mortality, mechanical ventilation, and ICU utilization. Survey-weighted linear regression estimated adjusted differences in length of stay (LOS) and total charges. Models adjusted for age group, sex, race/ethnicity, primary payer, hospital bed size, hospital region, and comorbidity burden using vwcheck (van Walraven score derived from Elixhauser comorbidities). Results: In the complete-case regression cohort (weighted N=1,011,365), severe sepsis was associated with higher in-hospital mortality versus no sepsis (aOR 1.49, 95% CI 1.44–1.54), and septic shock with markedly higher mortality (aOR 4.75, 95% CI 4.63–4.87). Sepsis severity strongly predicted escalation of care: mechanical ventilation (severe sepsis aOR 1.37, 95% CI 1.24–1.50; septic shock aOR 6.31, 95% CI 5.93–6.71) and ICU utilization (severe sepsis aOR 1.07, 95% CI 1.03–1.11; septic shock aOR 6.44, 95% CI 6.26–6.62). Relative to the Northeast, adjusted mortality odds were lower in the Midwest (aOR 0.72), South (aOR 0.77), and West (aOR 0.81). Septic shock was associated with higher resource use (+1.38 LOS days; +$56,975 charges). Conclusions: In hospitalized patients with metastatic cancer, increasing sepsis severity was independently associated with stepwise increases in mortality, need for ICU-level care, and healthcare utilization. Patients with septic shock represented a particularly high-risk subgroup, with markedly elevated mortality and resource use even after adjustment for comorbidity burden. These findings emphasize that sepsis, rather than malignancy alone, is a major driver of inpatient outcomes in advanced cancer and highlight the importance of early recognition and timely escalation of supportive care for this vulnerable population. Association of sepsis severity with inpatient outcomes among metastatic cancer hospitalizations (NIS 2016–2020). Outcome Severe sepsis (aOR or Δ, 95% CI) Septic shock (aOR or Δ, 95% CI) In-hospital mortality 1.49 (1.44–1.54) 4.75 (4.63–4.87) Mechanical ventilation 1.37 (1.24–1.50) 6.31 (5.93–6.71) ICU utilization 1.07 (1.03–1.11) 6.44 (6.26–6.62) Length of stay, days −0.42 +1.38 Total hospital charges, $ −3,325 +56,975
SHR-1826, a c-MET directed antibody-drug conjugate (ADC), in advanced solid tumors: Updates from a phase 1 study.
8525 Background: SHR-1826 is a novel ADC comprising a humanized IgG2 monoclonal antibody targeting c-MET, conjugated via a cleavable peptide-based linker to a topoisomerase I inhibitor payload. We conducted a multi-center, first-in-human, phase 1 trial of SHR-1826 in patients with advanced solid tumors. Here we report updated results, with a focus on patients with EGFR -mutated ( EGFRmut ) lung adenocarcinoma (LUAD). Methods: The study consisted of dose-escalation (i3+3 design), dose-expansion and efficacy-expansion phases. Patients with advanced solid tumors harboring MET alterations, who had failed standard therapy or had no available standard treatment options, were enrolled and received SHR-1826 intravenously at 2.2–6.0 mg/kg Q3W. In patients with EGFRmut LUAD, 4.0 and 5.0 mg/kg Q3W were evaluated during dose and efficacy expansion. Results: As of Dec. 3, 2025, 195 patients with lung (n=126), colorectal (n=40), gastric (n=22), liver (n=5), or pancreatic (n=2) cancer were treated. Median age was 59.0 yrs; 89.7% had ECOG performance status 1. Among 36 patients with EGFRmut LUAD, median number of prior lines of therapy was 2 (range 1–9); 97.2% had previously received EGFR-TKI (3 rd generation, 88.9%) and 75.0% received platinum-based chemotherapy. As of data cutoff, median follow-up was 14.4 months. Efficacy in EGFRmut LUAD across doses is shown in Table 1. Overall, the confirmed objective response rate (ORR) was 41.7% (95% CI 25.5–59.2) and median duration of response (DoR) was 14.1 months (95% CI 5.6–not reached [NR]). Median progression-free survival (PFS) was 9.8 mo (95% CI 5.8–15.4). Median overall survival (OS) was not reached; 12-month OS rate was 67.4% (95% CI 48.9–80.5). In all 195 patients, grade ≥3 treatment-related adverse events (TRAEs) were reported in 129 patients (66.2%), with all occurring in ≥5% being hematological toxicities. Interstitial lung disease occurred in 4 (3.1%; grade ≥3, n=2 [1.6%]) patients. TRAEs led to treatment discontinuation in 8 (4.1%) patients. No treatment-related deaths were reported. Conclusions: SHR-1826 demonstrated encouraging activity with manageable safety in heavily pretreated patients with MET-altered EGFRmut LUAD. Multiple trials are ongoing to assess SHR-1826 combined with other anti-tumor therapies in NSCLC. Clinical trial information: NCT06094556 . Efficacy outcomes in EGFRmut LUAD. 4.0 mg/kg (n=16) 5.0 mg/g (n=18) All patients (n=36) Confirmed ORR (n/N; 95% CI), % 31.3 (5/16; 11.0–58.7) 50.0 (9/18; 26.0–74.0) 41.7 (15/36; 25.5–59.2) DCR (n/N; 95% CI), % 87.5 (14/16; 61.7–98.4) 100.0 (18/18; 81.5–100.0) 94.4 (34/36; 81.3–99.3) Median DoR (95% CI), mo NR (8.6–NR) 9.7 (4.2–NR) 14.1 (5.6–NR) Median PFS (95% CI), mo 12.4 (2.6–NR) 8.4 (4.5–15.4) 9.8 (5.8–15.4) 12-mo OS (95% CI), % 67.0 (37.9–84.7) 69.1 (40.7–85.9) 67.4 (48.9–80.5) Data are based on the full analysis set. DCR, disease control rate.
Belzutifan in docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): Phase 1b/2 KEYNOTE-365 cohort J.
5058 Background: Hypoxia-inducible factor 2α (HIF-2α) is an established oncogenic driver, and HIF-2α expression in prostate cancer is positively correlated with aggressive disease. Belzutifan is a selective HIF-2α inhibitor approved for use in clear cell renal cell carcinoma. Cohort J of the multicohort, phase 1b/2 KEYNOTE-365 study (NCT02861573) evaluated the safety and efficacy of belzutifan in participants (pts) with mCRPC. Methods: Eligible adults had histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology, had an Eastern Cooperative Oncology Group performance status score of 0 or 1, and had received prior docetaxel for mCRPC. Prior treatment with 1 other chemotherapy and ≤2 second-generation hormonal agents were allowed. Pts received oral belzutifan 120 mg daily. Primary end points were safety and tolerability, prostate-specific antigen (PSA) response rate (PSA decline ≥50%), and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included time to PSA progression, ORR, and radiographic progression-free survival (rPFS) per PCWG3-modified RECIST v1.1, duration of response and disease control rate (DCR; complete response + partial response + stable disease ≥6 mo) per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR, and overall survival (OS). Results: A total of 21 pts were allocated to receive belzutifan. Median age was 69.0 y (range, 56-84). Median study follow-up was 17.6 mo (range, 15.9-21.8). All pts discontinued treatment as of the data cutoff (August 25, 2025), most commonly due to progressive disease (n = 12; 57%). Median duration of belzutifan therapy was 2.8 mo (range, 0.7-8.7). Treatment-related adverse events (AEs) occurred in 20 pts (95%); grade 3 or 4 treatment-related AEs occurred in 11 pts (52%), most commonly anemia (n = 8; 38%). A total of 2 pts (10%) discontinued treatment, and no pts died due to treatment-related AEs. Among pts with a baseline PSA measurement (n = 20), PSA response rate was 0% (95% CI, 0-17) and median time to PSA progression was 3.0 mo (95% CI, 2.8-not reached [NR]). Among 12 pts with RECIST-measurable disease, ORR and DCR per RECIST v1.1 were both 0%; ORR and DCR per PCWG3-modified RECIST v1.1 were 0% and 8%, respectively. In all pts, median rPFS was 3.7 mo (95% CI, 1.9-NR) and median OS was 16.9 mo (95% CI, 10.8-NR). Conclusions: In cohort J of the KEYNOTE-365 trial, belzutifan monotherapy had a manageable safety profile but did not show meaningful antitumor activity in mCRPC. Future research is needed to determine effective treatments for pts with mCRPC. Clinical trial information: NCT02861573 .
Racial and insurance-based differences in nutritional anemia among hospitalized patients with head and neck cancer: A national analysis, 2016–2022.
e23200 Background: Nutritional compromise is a common and clinically important concern among patients with head and neck cancer, driven by tumor-related dysphagia, treatment-associated toxicity, and chronic inflammation. Nutritional anemia reflects both nutritional and physiologic vulnerability, yet its distribution across sociodemographic groups at the time of hospitalization remains poorly characterized. We aimed to evaluate sociodemographic factors, including race and insurance status, associated with nutritional anemia among adults hospitalized with head and neck cancer. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample (NIS) from 2016 to 2022, identifying adult hospitalizations with a principal diagnosis of head and neck cancer and nutritional anemia using ICD-10-CM codes. Associations among nutritional anemia, sociodemographics and hospital characteristics were evaluated using multivariable logistic regression. Survey weights were applied to generate national estimates. Results: An estimated 189,320 hospitalizations for head and neck cancer were identified, of which 1.2 percent were complicated by nutritional anemia. The prevalence of nutritional anemia varied by race and insurance status. After multivariable adjustment, Black race and Medicaid insurance were associated with higher odds of nutritional anemia compared with White race and private insurance, respectively. Patients from lower neighborhood income quartiles also had higher odds of nutritional anemia. In contrast, treatment at large or teaching hospitals was associated with lower odds of nutritional anemia. Age and sex were not independently associated with nutritional anemia after adjustment. Conclusions: Among hospitalized patients with head and neck cancer, nutritional anemia is not evenly distributed across sociodemographic groups. Racial and insurance-based differences persist after accounting for comorbidity burden and hospital characteristics, suggesting that nutritional vulnerability at hospital presentation may reflect broader structural and access-related factors. These findings support the need for earlier and more targeted nutritional assessment in populations at increased risk.
Survival outcomes with immune checkpoint inhibitors in patients with pre-existing autoimmune disease: A global federated database analysis.
e24171 Background: Patients with pre-existing autoimmune diseases (pAI) have historically been excluded from pivotal immune checkpoint inhibitor (ICI) clinical trials due to concerns regarding exacerbated toxicities and potentially diminished antitumor efficacy. Consequently, real-world data on the long-term survival of this population remains limited. This study aimed to determine if pAI impacts overall survival (OS) in patients receiving ICIs for advanced malignancies. Methods: Using the TriNetX Global Collaborative Network (170 healthcare organizations), we identified adult patients with advanced solid tumors treated with ICIs. The pAI cohort included patients with a diagnosis of rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, psoriasis, or Sjögren syndrome within one month prior to ICI initiation. From an initial pool of 198,224 controls and 8,629 pAI patients, a 1:1 propensity score match (PSM) was performed. Cohorts were balanced for age, sex, race, ethnicity, and comorbidities (diabetes, hypertension, atrial fibrillation). The primary endpoint was overall survival (OS) analyzed via Kaplan-Meier and Cox proportional hazards models. Results: PSM yielded two well-balanced cohorts of 7,132 patients each (N = 14,264). Baseline characteristics showed no significant differences after matching (p > 0.05). Median OS was 896 days in the pAI cohort compared to 882 days in the matched control cohort (Log-rank p = 0.168). The risk of mortality was equivalent between groups with a Hazard Ratio (HR) of 1.035 (95% CI, 0.985–1.088; p = 0.165). Five-year survival probabilities were 28.21% for the pAI group and 26.16% for the control group. Risk analysis further confirmed no significant difference in the total incidence of mortality (43.8% vs. 44.5%; p = 0.409). Conclusions: PSM yielded two well-balanced cohorts of 7,132 patients each (N = 14,264). Baseline characteristics showed no significant differences after matching (p > 0.05). Median OS was 896 days in the pAI cohort compared to 882 days in the matched control cohort (Log-rank p = 0.168). The risk of mortality was equivalent between groups with a Hazard Ratio (HR) of 1.035 (95% CI, 0.985–1.088; p = 0.165). Five-year survival probabilities were 28.21% for the pAI group and 26.16% for the control group. Risk analysis further confirmed no significant difference in the total incidence of mortality (43.8% vs. 44.5%; p = 0.409).