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Fungal oxidative stress tolerance depends on peroxiredoxin PrxA-mediated redox signaling to mitochondrial cytochrome c peroxidase Ccp1

A familiar paradox in a new exposure: Electronic cigarettes and thyroid cancer.

e22601 Background: Electronic cigarette (e-cigarette) use has increased rapidly in recent years, particularly among younger adults, yet its long-term oncologic implications remain poorly characterized. While combustible cigarette smoking has paradoxically been associated with a lower risk of thyroid cancer, potentially related to hormonal suppression and immunomodulatory effects, evidence regarding the association between e-cigarette use and thyroid cancer is limited. We evaluated the association between e-cigarette use and thyroid cancer in a large, diverse U.S. population. Methods: We performed a cross-sectional analysis of adults participating in the NIH All of Us Research Program. E-cigarette exposure was defined using self-reported survey data and categorized as ever versus never use, with additional stratification into never, former, and current use. The primary outcome was thyroid cancer, identified using validated electronic health record diagnosis codes from the All of Us Registered Tier Dataset (version 8). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between e-cigarette use and thyroid cancer. Models accounted for age, sex, race and ethnicity, body mass index, alcohol use, and traditional cigarette smoking. Results: Among over 300,000 participants, 29,343 (8.9%) reported e-cigarette use. Compared with non-users, e-cigarette users were significantly younger (mean age: 45.2 vs 59.1 years) and differed across sex, race, and ethnicity, and multiple socioeconomic characteristics (p<0.001). After multivariable adjustment, ever e-cigarette use was associated with lower odds of thyroid cancer (OR 0.79, 95% CI 0.66-0.94). Current e-cigarette use demonstrated a stronger inverse association (OR 0.66, 95% CI 0.45-0.94), whereas former use was not statistically significant. Conventional cigarette smoking was independently associated with lower odds of thyroid cancer. No significant interaction between e-cigarette use and smoking status was observed. Conclusions: In this large population-based analysis, e-cigarette use was independently inversely associated with thyroid cancer after adjustment for established risk factors, mirroring prior observations reported for combustible cigarette smoking. These findings should not be interpreted as endorsement of e-cigarette use but suggest that nicotine-related or immunomodulatory pathways common to both exposures may influence thyroid carcinogenesis. Further prospective and mechanistic studies are needed to clarify causality and identify potential targets that can be leveraged without the harms associated with nicotine exposure.

Supporting treatment resilience with optimized nutrition and guided exercise (STRONGER) in head and neck cancer patients undergoing chemoradiation.

TPS12161 Background: Patients with head and neck cancer (HNC) undergoing concurrent chemoradiation (chemoRT) frequently experience debilitating toxicities, including mucositis, dysphagia, fatigue, and anorexia. These treatment-related effects are associated with weight loss, sarcopenia, and functional decline, which may adversely impact treatment adherence and quality of life. Although patients commonly seek lifestyle-based supportive interventions, evidence-based, structured multimodal programs integrated during active chemoradiation remain limited. The STRONGER pilot study was designed to evaluate the feasibility and acceptability of an integrated nutrition, guided exercise, and wellness education intervention aimed at supporting treatment resilience and characterizing functional and body composition changes in this population. Methods: STRONGER is a single-arm pilot study enrolling up to 30 adult patients with biopsy-confirmed squamous cell carcinoma of the head and neck undergoing definitive or adjuvant chemoRT at Renown Health and the William N. Pennington Institute for Cancer. Eligible participants have an ECOG performance status of 0 to 2 and are able to participate in light-to-moderate physical activity. Patients with severe malnutrition, defined by Global Leadership Initiative on Malnutrition criteria and greater than 90% caloric intake via enteral feeding, or with comorbidities precluding safe exercise participation, are excluded. The 20-week multimodal intervention begins at pre-treatment baseline and continues through three months post-chemoRT, incorporating individualized nutrition counseling with calorie and protein targets informed by indirect calorimetry, twice-weekly virtual home-based resistance and mobility training with prescribed daily walking goals, and structured wellness programming, including facilitated group sessions focused on stress and fatigue management and a speech-language pathology education series. The primary objective is to assess feasibility and acceptability, defined by prespecified thresholds for recruitment, retention, and intervention adherence, as well as participant-reported acceptability measured using Likert-scaled surveys. Secondary exploratory outcomes include measures of body composition, physical function, and patient-reported quality of life and symptom burden assessed using validated instruments. Descriptive statistics and exploratory paired analyses will be used to characterize within-participant changes over time. Enrollment is ongoing. As of January 24, 2026, 2 of 30 planned participants have been enrolled. Clinical trial information: NCT07160296 .

Pilot trial of virtual and in-person symptom screening with targeted early palliative care (STEP2).

12074 Background: Routine early palliative care (EPC) for patients with advanced cancer improves quality of life. To increase scalability, models of triggered EPC have been encouraged. We assessed feasibility of hybrid virtual/in person Symptom screening and Targeted Early Palliative care (STEP2) to provide EPC triggered by symptoms. Methods: Patients with advanced cancer, ECOG 0-2, prognosis 6-36 months, were recruited from lung, gastrointestinal, genitourinary, breast and gynecology outpatient oncology clinics. Symptoms were screened virtually/in person ≤48 hours before oncology visits using Edmonton Symptom Assessment System-revised (ESAS-r+). Moderate to severe symptom scores (“screen positive”) triggered an alert to a nurse, who called the patient, offering an EPC visit (in-person/virtual, as per patient preference). Participants completed measures at baseline, 2, 4, and 6 months. The primary endpoint was feasibility, with the following criteria: ≥40 patients accrued in 4 months; ≥60% complete screening for ≥70% of visits; ≥50% triggering a call have ≥1 EPC visit; ≥60% complete all measures. Results: From 30/03/2025-26/06/2025 40 patients were enrolled (median age [range], 62 [39-88]; 21/40 [53%] female). Disease site distribution was: 12/40 (30%) lung, 9/40 (23%) gynecology, 8/40 (20%) genitourinary, 6/40 (15%) gastrointestinal, 5/40 (13%) breast. Of the 40 patients enrolled, 36 (90%) completed screening for ≥70% of visits and 29 (73%) screened positive: 18 at baseline and 11 later during the trial. The most common triggering symptoms were anxiety (18/29, 62%), sleep (17/29, 59%), depression (10/29, 35%), pain (8/29, 28%), and dyspnea (8/29, 28%); 21/29 (72%) screen-positive and 0 screen-negative patients received EPC before trial end. Measure completion at 2, 4, and 6 months was 90% (36/40), 85% (34/40), and 83% (33/40). Initial EPC visits were in person for 14/21 (67%) and virtual for 7/21 (33%); 20/21 (95%) of patients received ≥2 follow-up visits. Results for measures at baseline and at trial end are shown in the Table. Conclusions: Virtual/in person STEP2 is feasible and directs EPC to those who most need it, with most screen-positive patients accepting EPC. A phase III trial is underway. Clinical trial information: NCT06326554 . Variable Measure (score range) Time point N Mean Standard Deviation Difference, 6 mo. vs. baseline (95% CI) Quality of life FACIT_PAL14 Baseline 40 42.2 7.2 0.3 (0-56; higher is better) 6 mo. 34 42.7 7.7 (-0.9, 1.6) Symptom ESAS_EDS Baseline 40 17.5 12.9 0.3 Control (0-90; higher is worse) 6 mo. 33 18.9 13.2 (-3.1, 3.7) Depression PHQ-9 Baseline 40 5.4 3.4 -1.0 (0-27; higher is worse) 6 mo. 34 4.6 3.1 (-1.9, 0.0) Anxiety GAD-7 Baseline 40 4.9 3.8 -1.4 (0-21; higher is worse) 6 mo. 34 3.7 3.5 (-2.3, -0.5) Satisfaction FAMCARE-P16 Baseline 40 72.8 7.2 -5.8 With care (16-80; higher is better) 6 mo. 34 67.1 12.0 (-10.1, -1.4)

Early vs delayed bone-modifying agent initiation and zoledronic acid vs denosumab in newly diagnosed multiple myeloma.

e19573 Background: Bone-modifying agents (BMAs) reduce skeletal-related events (SREs) in multiple myeloma, but real-world practice varies in both initiation timing and agent selection. Methods: Using the TriNetX Research network (2012–2024), adults with multiple myeloma initiating systemic therapy who received a BMA. Patients were categorized as early (≤60 days) vs delayed (61–180 days) BMA initiation relative to systemic therapy start. A 60-day landmark from systemic therapy initiation was applied to minimize immortal time bias. In a separate analysis, zoledronic acid (ZA)-only and denosumab-only users were compared. Cohorts were 1:1 propensity-score matched on demographics, comorbidities, renal function/CKD stage, baseline bone disease and prior SREs, myeloma treatment (including ASCT), and key laboratory values (including creatinine, calcium, and albumin). Outcomes included 1-year SRE risk and time-to-first SRE (Kaplan–Meier/Cox). Because median time-to-SRE was not reached, restricted mean time to first SRE (RMST) at 1 year was reported. Secondary safety outcomes included overall survival (OS) and safety outcomes (renal toxicity and hypocalcemia, lab-based when available, within 90 days; osteonecrosis of the jaw [ONJ] through 10 years). Results: After matching, 1,799 patients per cohort were included in the early versus delayed initiation analysis. Early initiation was associated with a lower 1-year SRE risk (16.0% vs 19.5%; p=0.0068) and a longer RMST to first SRE (315 vs 309 days). There was no significant difference in 10-year OS (49.7% vs 52.3%; p=0.2077), although 5-year OS was modestly higher with early initiation (71.3% vs 67.2%; p=0.0454). In the agent comparison, 1,233 matched patients per cohort received ZA or denosumab. There were no significant differences in 1-year SRE risk (21.7% vs 19.6%; p=0.196) or overall survival at 5 or 10 years. Renal toxicity within 90 days was lower with ZA (19.5% vs 25.8%; p=0.0002), while hypocalcemia rates were similar (60.6% vs 62.4%; p=0.341). ONJ events were infrequent but occurred less often with ZA (event-free probability at 10 years: 96.6% vs 95.3%; p=0.0068). Conclusions: In this large real-world cohort, initiating BMAs within 60 days of systemic therapy was associated with fewer early SREs compared with initiation at 61–180 days, without a difference in long-term survival. Zoledronic acid and denosumab demonstrated similar SRE and OS outcomes, supporting individualized agent selection, with distinct renal and ONJ safety profiles.

Impact of sustained MRD negativity for up to 5 years on long-term outcome of transplant-eligible newly diagnosed multiple myeloma patients enrolled in the randomized phase 2 FORTE trial.

7504 Background: Novel combinations induce high rates of minimal residual disease (MRD) negativity (neg) in multiple myeloma (MM) patients (pts). However, the optimal duration of MRD negative status to predict long term outcomes remains a matter of debate. We analyzed the impact of different sustained (sust) MRD neg cut-offs on progression free survival (PFS) and overall survival (OS) in transplant eligible Newly Diagnosed MM pts treated in the randomized phase 2 FORTE trial (NCT02203643). Methods: We included all pts enrolled in the trial who were randomized to maintenance. MRD was assessed in the bone marrow in pts with ≥very good partial response by multiparameter flow cytometry (sensitivity of 10 -5 ) at premaintenance and every 6 months thereafter. SustMRD neg was defined as consecutive MRD-negative evaluations for at least 1, 2, 3, 4 or 5 years without intercurrent MRD-positive results. The primary aim of the analysis was the impact of different SustMRD neg durations on PFS. A subgroup analysis according to a modified Consensus Genomic Staging (mCGS as described in Avet-Loiseau et al JCO 2025 without the use of molecular data), and the presence of an MGUS-like profile at diagnosis (Burgos et al JCO 2023) was performed. Results: 356 pts were randomized to maintenance according to study protocol. After a median follow-up of 85 months from maintenance randomization, 77% of pts have > 1 MRD negative evaluation. The rate of at least 1, 2, 3, 4, 5-years sustMRD neg was 53%, 42%, 36%, 28% and 20% respectively. Compared to MRD positive patients (n=83), MRD neg lasting <1 year (HR 0.72; 95% CI 0.47-1.09), 1 year (HR 0.40; 95% CI 0.22-0.72), 2 years (HR 0.36; 95% CI 0.19-0.66), 3 years (HR 0.17; 95% CI 0.07-0.40), 4 years (HR 0.15; 95% CI 0.06-0.35) and 5 years (HR 0.06; 95% CI 0.03-0.15) significantly and progressively improved pts’ PFS. In pts with ≥ 3-years sustMRD neg vs < 3-year sustMRD, 7-years PFS rates were 84.7% vs 35.4% (HR 0.16, 95% CI 0.10-0.27) and 7-years OS rates were 97% vs 69% (HR 0.08, 95% CI 0.02-0.27). Stratifying patients according to mCGS and 3-years sustMRD neg, 7-years PFS rates were 84% for mCGS standard risk with ≥ 3-y sustMRD, 83% for mCGS high risk and ≥ 3-y sustMRD, 43% for mCGS standard risk with < 3-y sustMRD, 23% for mCGS high risk with < 3-y sustMRD. Among patients with < 3-years sustMRD neg, the presence of an MGUS-like profile predicted a significantly better PFS and OS compared to non MGUS-like pts (7-years PFS 67% vs 33%, HR 0.37 95% CI 0.17-0.85; 7-years OS 93% vs 66%, HR 0.15 95% CI 0.02-1.08). Conclusions: SustMRD neg for more than 3 years significantly improved PFS and OS of NDMM pts, with pts with at least 5-year SustMRD neg having a 7-year PFS of 91%. Reaching > 3-y sustMRD neg is mandatory in high-risk pts to achieve long term remissions, while MGUS-like pts may have good outcomes despite the absence of 3-y sustMRD neg. Clinical trial information: NCT02203643 .

Comparative inpatient outcomes among FDA-approved chimeric antigen receptor T-cell products: An analysis of the 2023 National Inpatient Sample.

e23088 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed or refractory hematologic malignancies. National data comparing inpatient outcomes among different CAR-T products is limited. The CMS introduced ICD10-PCS procedure codes for individual CAR-T products that went into effect on October 1st, 2021. Leveraging these codes, we conducted a national analysis of real-world inpatient outcomes associated with FDA-approved CAR-T therapies in 2023. Methods: We conducted a retrospective cross-sectional study using the 2023 Healthcare Cost and Utilization Project National Inpatient Sample. Hospitalizations involving CAR-T therapy were identified using ICD-10-PCS procedure codes. The primary outcome was a composite measure of severe inpatient toxicity, defined as the occurrence of any of the following: in-hospital mortality, mechanical ventilation, clinically significant cytokine release syndrome (CRS), or clinically significant immune effector cell-associated neurotoxicity syndrome (ICANS). Secondary outcomes included individual components of the composite, and tumor lysis syndrome (TLS). National estimates were generated using discharge-level survey weights. Pairwise comparisons were performed using the Rao-Scott chi-square test with Bonferroni correction for multiple comparisons. Statistical analysis was conducted using the SAS software (SAS Institute, Cary, NC). Results: A total of 1,117 (weighted N = 5,585) inpatient CAR-T hospitalizations occurred nationally in 2023. The mean age was 61 years with 62% being male. Underlying indications included Large B-Cell Lymphoma (40%), Multiple Myeloma (28.9%), Acute Lymphoblastic Leukemia (7.3%) and other hematologic malignancies. The composite severe toxicity outcome occurred in 27.8% of hospitalizations. Clinically significant CRS and clinically significant ICANS occurred in 18.1% and 14.8%, respectively, while 2.1% required mechanical ventilation and TLS occurred in 1.6% of hospitalizations. The in-hospital mortality rate was 1.9%. Compared with Axi-cel, Cilta-cel (aOR 0.51), Ide-cel (aOR 0.50), and Liso-cel (aOR 0.59) were associated with significantly lower odds of the composite outcome (p < 0.01). Compared with Axi-cel, Cilta-cel (aOR 0.15), Ide-cel (aOR 0.30), and Liso-cel (aOR 0.33) were associated with significantly lower odds of ICANS (p < 0.01). Conclusions: In this national analysis of CAR-T hospitalizations, substantial heterogeneity in severe toxicity and neurotoxicity was observed across FDA-approved CAR-T products. Compared with Axi-cel, several newer CAR-T therapies were associated with significantly lower odds of severe toxicity and neurotoxicity in real-world practice, highlighting important product-specific differences that may inform risk stratification and clinical decision making.

Trends in mortality due to lung cancer in patients with respiratory tract infections in the United States, 1999–2023: A CDC population-based analysis.

e20061 Background: Lung cancer remains the leading cause of cancer-related mortality in the United States. Respiratory tract infections (RTIs) are common complications among patients with lung cancer due to immunosuppression, airway obstruction, and treatment-related toxicity, and are associated with worsened clinical outcomes. Despite the clinical relevance of RTIs in lung cancer care, national-level evaluations of long-term mortality trends among lung cancer patients with concurrent RTIs remain limited. This population-based study examines temporal trends, demographic disparities, and geographic variation in lung cancer–related mortality among patients diagnosed with RTIs in the United States from 1999 to 2023. Methods: Mortality data were obtained from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database for the years 1999–2023. Deaths were identified using ICD-10 codes with lung cancer listed as the underlying cause of death and respiratory tract infection recorded as a contributing condition. Analyses were stratified by calendar year, sex, race and ethnicity, age, place of death, urbanization status, and U.S. census region. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population with corresponding 95% confidence intervals. Temporal trends were evaluated using Joinpoint regression to estimate the average annual percent change (AAPC). Results: Between 1999 and 2023, a total of 222,792 lung cancer–related deaths were identified among patients with RTIs in the United States, with the majority occurring in medical facilities (128,308 deaths). The overall AAMR declined substantially from 3.85 per 100,000 in 1999 to 1.94 per 100,000 in 2023, corresponding to an AAPC of -2.54 (95% CI, -3.63 to -1.45), though a modest increase was observed during 2021–2022. Men experienced a higher average AAMR than women (3.71 vs 1.84), with a steeper decline over time among men (AAPC -3.57 vs -1.56). By race and ethnicity, non-Hispanic Black individuals had the highest AAMR (3.09), while Hispanic individuals had the lowest (1.38). Mortality rates were higher in non-urban areas (AAMR 3.25; AAPC -2.79) compared with urban areas (AAMR 2.51; AAPC -3.23). Regionally, the South exhibited the highest AAMR (2.84), while the West had the lowest (2.38). Conclusions: Lung cancer mortality among patients with RTIs declined significantly in the United States from 1999 to 2023; however, persistent disparities by sex, race and ethnicity, geographic region, and urbanization remain. These findings underscore the need for targeted infection prevention strategies, equitable access to pulmonary and oncologic care, and focused interventions for vulnerable populations, particularly during periods of healthcare system strain.

Immune checkpoint inhibitors and respiratory outcomes in cancer patients with pre-existing asthma: A TriNetX propensity-matched cohort study.

11150 Background: Immune checkpoint inhibitors (ICIs) are associated with immune-related pulmonary toxicity. Real-world data on outcomes in patients with pre-existing asthma across malignancies remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (170 HCOs). Adults (≥18 years) with asthma (ICD-10 J45) and malignancy (ICD-10 C00–C96) were identified. The ICI cohort included patients receiving ICIs (HCPCS J9271, J9299, J9119, J9272, J9345, J9022, J9173, J9023, J9228, J9347) after cancer diagnosis (first ICI within 3 years of first malignancy). The comparator cohort included patients receiving non-ICI systemic therapy (TNX:1002 chemotherapy, TNX:1003 targeted therapy, TNX:1004 hormone therapy, and/or Z51.11) and excluded ICI exposure. Outcomes were assessed from day 1 through day 1095 after index. Propensity score matching (1:1) was performed (final N = 4,074 per cohort). Results: In the matched cohorts (N = 4,074 each), ICI exposure was associated with higher risks of inpatient admissions (41.65% vs 32.78%; RR 1.27; HR 1.22), all-cause mortality (47.62% vs 38.76%; RR 1.23; HR 1.44), respiratory failure (J96) (25.01% vs 15.13%; RR 1.65; HR 1.66), and drug-induced interstitial lung disorders (1.91% vs 0.87%; RR 2.20; HR 4.26). ICI exposure was also associated with increased risk of mechanical ventilation (4.00% vs 2.93%; RR 1.36; HR 1.45), emergency intubation (2.55% vs 2.00%; RR 1.27; HR 1.32), and ED visits (38.98% vs 31.56%; RR 1.24; HR 1.74). Asthma exacerbation (J45.901) showed a modest increase in risk (RR 1.23), with survival analysis not reaching statistical significance (HR 1.15; p = 0.078). Conclusions: Among adults with asthma and cancer, ICI exposure was associated with increased risks of hospitalization, respiratory failure, drug-induced interstitial lung disorders, and mortality compared with non-ICI systemic therapy. These findings support close pulmonary monitoring and risk mitigation when initiating ICIs in patients with asthma.

Association of prophylactic G-CSF use with survival outcomes in patients with aggressive B-cell lymphomas treated with R-CHOP.

e19061 Background: R-CHOP is the standard first-line regimen for aggressive CD20-positive B-cell lymphomas, including diffuse large B-cell lymphoma. Outcomes depend on maintaining chemotherapy dose intensity, but myelosuppression and febrile neutropenia (FN) frequently lead to treatment delays or dose reductions. Prophylactic granulocyte colony-stimulating factors (G-CSFs) reduce FN risk and preserve dose intensity and are guideline-recommended for patients at moderate-to-high FN risk; however, evidence for improved long-term survival in real-world R-CHOP–treated populations remain limited. We evaluated the association between prophylactic G-CSF use and survival and safety outcomes using a multi-institutional electronic health record network. Methods: We conducted a retrospective study using the TriNetX research network from 2012-2024. Adults with aggressive B-cell lymphomas who received R-CHOP were grouped based on whether or not they received prophylactic G-CSF within 3-days of cycle 1. Propensity score matching was used to balance cohorts before comparing survival using a Kaplan-Meier survival analysis. Secondary outcomes included early neutropenia and septic shock or vasopressor use. Results: After propensity score matching, 4,007 patients receiving R-CHOP with G-CSF were well balanced with 4,007 patients receiving R-CHOP without G-CSF across baseline characteristics. At 6 months, mortality was 6.20% with G-CSF versus 7.33% without (risk difference −1.13%, 95% CI −2.23% to −0.02%; HR 0.84, 95% CI 0.71–0.99; p = 0.045). At 12 months, mortality was 10.20% vs 11.42% (risk difference −1.22%, 95% CI −2.58% to 0.15%; HR 0.88, 95% CI 0.77–1.00; p = 0.08), and at 24 months remained lower with G-CSF (13.48% vs 15.10%; risk difference −1.63%, 95% CI −3.16% to −0.09%; HR 0.87, 95% CI 0.78–0.98; p = 0.038). Survival probabilities favored G-CSF at 6 months (93.7% vs 92.5%), 12 months (89.4% vs 88.1%), and 24 months (85.6% vs 83.7%). Neutropenia was more frequently documented with G-CSF (28.7% vs 26.7%; HR 1.13, 95% CI 1.04–1.23; p < 0.001) but not after excluding patients with prior neutropenia (22.45% vs 23.03%; HR 1.02, 95% CI 0.93–1.13; p = 0.56). Rates of septic shock (1.20% vs 1.22%; HR 0.98, 95% CI 0.66–1.46; p = 0.91) and septic shock or vasopressor use were low and similar between groups, including in sensitivity analyses. Conclusions: In this large real-world, propensity-matched cohort of patients with B-cell lymphomas treated with R-CHOP, prophylactic G-CSF use was associated with improved early and long-term survival without a difference in septic shock or severe infectious complications. Apparent increases in neutropenia were not observed after accounting for baseline history, suggesting no excess risk of new-onset neutropenia. These findings support the routine use of G-CSF with R-CHOP and suggest a potential survival benefit beyond neutropenia prevention.

Izalontamab brengitecan (iza-bren) versus chemotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC): A multicenter, randomized, open-label, phase III study.

4008 Background: Chemotherapy plus a PD-1/PD-L1 inhibitor is the standard first-line treatment for PD-L1 expressing advanced ESCC. However, most patients (pts) inevitably develop resistance to first-line therapy, and second-line chemotherapy shows an ORR of less than 10% and a median OS of less than 6 mo, highlighting the urgent need for novel therapeutics. Iza-bren is a potentially first-in-class ADC consisting of an EGFR-HER3 bispecific antibody conjugated to a potent topoisomerase I inhibitor Ed-04 via a cleavable linker. Iza-bren has shown promising clinical activity in previously treated ESCC pts in phase I study. Here, we present results from a phase III, randomized, open-label, multicenter study conducted in China evaluating the efficacy and safety of iza-bren versus chemotherapy as second line treatment for advanced ESCC. Methods: Pts with recurrent or metastatic ESCC who had progressed after first-line treatment with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy were randomized (1:1) to receive iza-bren (2.5 mg/kg at D1D8 Q3W) or physician’s choice of chemotherapy (irinotecan, paclitaxel, or docetaxel Q3W). Dual primary endpoints were OS and PFS by Blinded Independent Central Review (BICR) per RECIST v1.1. Results: As of Oct 17, 2025, a total of 497 pts were randomized to iza-bren (n = 249) or chemotherapy (n = 248). Baseline characteristics were balanced between the two groups. At interim analysis, median follow-up for OS was 7.8 mo in the iza-bren group and 7.6 mo in the chemotherapy group. Iza-bren has demonstrated statistically significant and clinically meaningful improvement in both OS and PFS by BICR compared with chemotherapy. The median OS was 9.8 mo (95% CI, 7.9 to 11.0) with iza-bren and 7.2 mo (95% CI, 6.2 to 8.2) with chemotherapy (HR, 0.64; 95% CI, 0.49 to 0.83; P = 0.0004). The median PFS by BICR was 4.2 mo (95% CI, 3.6 to 4.5) with iza-bren and 2.0 mo (95% CI, 1.6 to 2.7) with chemotherapy (HR, 0.50; 95% CI, 0.40 to 0.63; P < 0.0001). ORR by BICR was 35.3% for iza-bren and 13.1% for chemotherapy. Grade≥3 TRAEs, which were predominantly hematologic in nature, occurred in 85.1% in the iza-bren group and 60.2% in the chemotherapy group. TRAEs leading to drug discontinuation were 2.0% in the iza-bren group and 3.3% in the chemotherapy group. TRAEs leading to death were 1.2% in the iza-bren group and 1.6% in the chemotherapy group. Conclusions: The study met both dual primary endpoints at prespecified interim analysis. Iza-bren demonstrated statistically significant and clinically meaningful improvements in OS and PFS compared with chemotherapy in pts with recurrent or metastatic ESCC who had progressed after first line PD-1/PD-L1 inhibitor plus platinum-based chemotherapy. The safety profile was manageable. The results support iza-bren as a new second-line standard of care for ESCC. Clinical trial information: NCT06304974 .

Mutation landscape and pathway-level disparities in Black versus White patients with acute myeloid leukemia.

6534 Background: Racial disparities in acute myeloid leukemia (AML) outcomes are well-documented, yet race- specific genomic differences remain incompletely characterized. Current risk stratification systems, developed from European-ancestry cohorts, may inadequately classify patients (pts) of African ancestry (Stiff, Nature Genetics , 2024). We performed comprehensive clinicogenomic analysis to identify race-specific mutation patterns and their clinical impact in AML. Methods: We analyzed genomic and outcomes data on AML pts in AACR Project GENIE database. Mutation frequencies, co-mutation patterns, and pathway alterations were compared between racial groups. Survival analyses used Cox proportional hazards models adjusted for age and sex. Multiple comparison correction used Benjamini-Hochberg false discovery rate (FDR). Results: Our study included 2,359 pts (Black, n=243; White, n=2,116). Black pts demonstrated a distinct mutational landscape with fewer splicing factor ( SRSF2, U2AF1, SF3B1 ) mutations (11.1% vs 20.1%, FDR p=0.003) and tumor suppressor ( TP53, WT1 ) mutations (11.9% vs. 18.2%, FDR p=0.038). Signaling/RAS pathway mutations were nominally higher in Blacks. A notable finding was the emergence of MDS-related gene mutations in Black pts at a younger age, suggesting distinct disease biology. Among pts aged <40 years, ASXL1 mutations were more prevalent in Blacks (10.2% vs. 1.8%, p=0.006). Co-mutation architectures differed substantially by race: in Black pts, ASXL1 and RUNX1 frequently co-occurred with RAS/MAPK pathway mutations (ASXL1+RAS: 7.8% vs. 3.4%, FDR p=0.006), whereas White pts had predominant co-occurrence of ASXL1 and RUNX1 with splicing factor mutations Critical survival disparities emerged by mutation status. NPM1+FLT3 co-mutation was less common in Blacks (3.3% vs. 7.0%, FDR p=0.028) and conferred markedly inferior survival when present (median OS 6.7 vs. 14.6 months, p=0.008). Strikingly, favorable-risk mutations showed race-specific effects. NPM1-only (HR 0.79, p=0.014), IDH1-only (HR 0.68, p=0.005), and NPM1+IDH1 (HR 0.61, p=0.013) were protective in White but not in Black pts: NPM1-only (HR 0.89, p=0.76), IDH1-only (HR 0.84, p=0.71), NPM1+IDH1 (HR 0.34, p=0.13), challenging current risk stratification's universal applicability. Overall survival (OS) was similar (median OS- 18 vs. 16.7 months), though propensity-matched analysis trended toward worse outcomes in Blacks (18 vs. 25 months, p=0.091). Conclusions: Black AML pts exhibit fundamentally distinct molecular biology with differential pathway involvement, earlier MDS-related mutations, unique co-mutation patterns, and loss of prognostic value for traditionally favorable mutations. These findings demonstrate that race-blind risk stratification may systematically misclassify Black pts, supporting urgent need for ancestry-informed precision medicine approaches in AML.

Risk of venous thromboembolism in lung cancer patients treated with chemotherapy versus immunotherapy: A propensity-matched TriNetX analysis.

e20070 Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with lung cancer. While immunotherapy has transformed lung cancer treatment, its association with thrombotic risk compared with conventional chemotherapy remains incompletely characterized. Methods: We conducted a retrospective cohort study using the TriNetX research network. Adult patients with lung cancer receiving either chemotherapy or immune checkpoint inhibitor–based immunotherapy were identified. The primary outcome was incident venous thromboembolism after treatment initiation. Cohorts were balanced using 1:1 propensity score matching based on demographics and clinical characteristics. Risk estimates and Kaplan–Meier survival analyses were performed. Results: A total of 311,380 chemotherapy-treated and 73,814 immunotherapy-treated patients were identified before matching. After propensity score matching, 66,011 patients remained in the chemotherapy cohort and 65,110 in the immunotherapy cohort with well-balanced baseline characteristics. Venous thromboembolism occurred in 2,262 chemotherapy patients (3.4%) and 2,524 immunotherapy patients (3.9%). Immunotherapy was associated with a modestly increased risk of VTE (risk ratio 1.06; odds ratio 1.07; p < 0.01). Kaplan–Meier analysis demonstrated lower VTE-free survival in the immunotherapy group (log-rank p < 0.0001), although proportional hazards assumptions were not met. Conclusions: In this large real-world analysis, immunotherapy was associated with a slightly increased risk of venous thromboembolism compared with chemotherapy in lung cancer patients. These findings highlight the importance of vigilant thrombotic risk assessment in patients receiving immune checkpoint inhibitors. Venous thromboembolism after matching. Treatment Events Total Patients Risk (%) Chemotherapy 2,262 66,011 3.4 Immunotherapy 2,524 65,110 3.9

Real-world outcomes of amivantamab monotherapy in advanced EGFR-mutant non-small cell lung cancer.

e20717 Background: Amivantamab, a bispecific EGFR/MET antibody, is approved for EGFR exon 20 insertion-mutant non-small cell lung cancer (NSCLC). However, real-world data evaluating it as monotherapy beyond exon 20 variants remain limited, as most retrospective series include combination therapy or heterogeneous settings. In clinical practice, some patients may receive monotherapy due to toxicity concerns, comorbidities, prior treatment tolerance, or physician/patient preference. We evaluated clinical outcomes of amivantamab monotherapy in a real-world cohort of patients with EGFR-mutant NSCLC. Methods: We conducted an IRB-approved retrospective review (Pro2025-0001) of patients with advanced EGFR-mutant NSCLC treated with amivantamab monotherapy in the second line or later between June 2021 and September 2024. Patients were categorized as classical (exon 19 deletion or L858R), atypical (eg, exon 18 or G719X), or exon 20 insertion (ex20ins), and unspecified variants. Analyses evaluated progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), time to next treatment (TTNT), overall survival (OS), and safety. Radiographic response was assessed by investigator review using RECIST v1.1. Time-to-event outcomes were censored at last assessment on or before September 30, 2024. Confidence intervals (CIs) were calculated using exact binomial methods for proportions and Kaplan-Meier methods for time-to-event endpoints. Results: Twenty-two patients met inclusion criteria; median age was 67.5 years (range, 42-82), and patients were heavily pretreated (median prior therapies, 2). Baseline CNS metastases were present in 36%. Mutation subgroups included 13 classical, 5 atypical, and 3 exon 20 insertions, and 1 unclassified variant. Twenty patients were evaluable for response. ORR was 25.0% (95% CI, 8.7-49.1) and DCR was 60.0% (95% CI, 36.1-80.9). ORR/DCR were 25%/75% in classical EGFR (3/12), 40%/40% in atypical EGFR (2/5), and 0%/33% in ex20ins (0/3), though subgroup estimates were limited by small sample size. Median PFS was 4.2 months (95% CI, 1.35-7.29). Median TTNT was 5.2 months. Median OS was 10.7 months (95% CI, 2.9-31.3) from amivantamab initiation and 35.4 months (95% CI, 25.8-74.0) from initial diagnosis. Median follow-up was 27.8 months. Grade ≥3 treatment-related adverse events occurred in 2 patients, including hyponatremia, peripheral edema, and infusion reaction. Intracranial progression occurred in 7 of 11 patients with evaluable CNS imaging (64%). Conclusions: In this heavily pretreated real-world cohort, amivantamab monotherapy demonstrated meaningful antitumor activity across diverse EGFR mutation subtypes, with outcomes comparable to prior trials and real-world experiences. These findings support consideration of amivantamab monotherapy beyond exon 20 insertions and warrant prospective evaluation in defined clinical settings.

Endothelin-1 levels in lung tissue of patients with non–small cell lung cancer with previous COVID-19 of varying severity.

e20045 Background: COVID-19 is a multisystem disease, largely due to vascular endothelial damage, and poses a risk to patients with non-small cell lung cancer (NSCLC), in whom the infection is more likely to progress to life-threatening conditions. Endothelin-1 (ET-1) is a potent vasoconstrictor, whose synthesis is induced by pulmonary infection and hypoxia. It has been shown that ET-1 is involved in the progression of the tumor process, but its role in patients with NSCLC who have recovered from COVID-19 remains unknown. The aim of research was to investigate the levels of endothelin-1 and its precursor in tissue of the tumor, perifocal zone and the resection line in patients with NSCLC who had previously suffered from COVID-19 of varying severity. Methods: The research included 80 patients of both sexes with verified NMSC of I-IIIA stages who had previously been infected with SARS-CoV-2. The main group consisted of 40 patients with severe/moderate severity COVID-19, while the control group included 40 patients with asymptomatic or mild cases. The content of ET 1-21 (active form) and ET 1-38 (precursor, non-active form) was determined using the ELISA method in tissue of the tumor, perifocal zone and the resection line. The Student's t-test as well as the Mann-Whitney test were used for statistical analysis. Results: The ratios of indicators in different zones of the lung tissue had sex differences. In men of the main group, the content of ET 1-21 was increased only in the perifocal zone of the tumor, by 1.9 times (p <0.05), and the level of ET 1-38 was increased in all studied zones by 1.5-2.6 times compared to the indicators in the control group. In the main group of women, the level of ET 1-21 was reduced by 2-2.7 times in the tumor and resection line tissue, while it did not differ from the control group in the perifocal zone, and the concentration of ET 1-38 was reduced by 4.9 times relative to this indicator in the control group only in the resection line tissue. Conclusions: Severe/moderate severity COVID-19 is associated with persistent changes in the ET-1 system in patients with NSCLC. Significant sex differences in the distribution of both forms of ET-1 in the lung tissue were found, which may reflect different mechanisms of the influence of SARS-CoV-2 on the tumor process in men and women. Particular attention should be paid to the pronounced accumulation of ET-1 in the perifocal zone of the tumor. It may contribute to the activation of angiogenesis and the progression of the disease.

Efficacy and safety of efbemalenograstim alfa versus PEG-rhG-CSF in preventing neutropenia in patients with locally advanced nasopharyngeal carcinoma undergoing induction chemotherapy followed by concurrent chemoradiotherapy.

e18064 Background: Preventing chemotherapy-induced neutropenia (CIN) is critical in locally advanced nasopharyngeal carcinoma (LA-NPC) management. Although PEG-rhG-CSF is widely used, evidence for the novel long-acting G-CSF efbemalenograstim alfa in LA-NPC remains limited. This study compares the efficacy and safety of efbemalenograstim alfa versus PEG-rhG-CSF for CIN prevention in LA-NPC. Methods: This retrospective study included stage III–IVa LA-NPC patients treated between July 2023 and April 2025. Based on the prophylactic G-CSF regimen received, patients were categorized into two groups: efbemalenograstim alfa and PEG-rhG-CSF. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics, yielding a final cohort of 126 patients (63 matched pairs). Prophylactic G-CSF was administered subcutaneously to both groups during gemcitabine plus cisplatin (GP) chemotherapy. In the induction chemotherapy (IC) phase, G-CSF was given 24 hours after gemcitabine infusion; during concurrent chemoradiotherapy (CCRT), it was administered 24 hours following cisplatin. The primary outcomes were the incidence and duration of grade 3–4 CIN. Secondary outcomes included the incidence of grade 4 CIN, febrile neutropenia (FN), changes of neutrophil count, chemotherapy completion rate, and safety. Results: Compared with PEG-rhG-CSF, efbemalenograstim alfa significantly shortened the duration of grade 3–4 CIN in the first IC cycle (1.7±0.76 days vs. 2.8±0.97 days, p=0.03) and maintained this benefit throughout subsequent IC and CCRT cycles. In the first IC cycle, the incidence of grade 3–4 CIN was 14.3% with efbemalenograstim alfa versus 19.0% with PEG-rhG-CSF (p=0.477), while the incidence of grade 4 CIN was 7.9% and 11.1% (p=0.548), respectively. The rate of FN was identical in both groups (4.7% vs. 4.7%, p=1.000). Over the entire treatment course, efbemalenograstim alfa was associated with significantly lower cumulative incidences of grade 3–4 CIN (15.8% vs. 31.7%, p=0.037) and grade 4 CIN (11.1% vs. 23.8%, p=0.032) compared to PEG-rhG-CSF. Both groups demonstrated a chemotherapy completion rate of 100%. Efbemalenograstim alfa was associated with a 6.4% lower delay rate and a 0.17-day reduction in average delay duration. It also demonstrated a superior safety profile, with significantly less bone pain (26.9% vs. 46.0%, p=0.019) and only mild-to-moderate adverse events. Conclusions: Efbemalenograstim alfa offers longer-lasting neutropenia protection than PEG-rhG-CSF in LA-NPC patients, resulting in shorter severe neutropenia, higher treatment compliance, and a better safety profile with less bone pain. These findings support its role as an effective and well-tolerated prophylactic option.

<i>EGFR</i> mutational landscape in non–small cell lung cancer: A 10-year experience of a national reference laboratory in Colombia (2014–2023).

e20565 Background: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases globally. Targeted therapies for patients harboring epidermal growth factor receptor (EGFR) mutations have revolutionized survival; however, ethnic and geographic variability in mutation prevalence remains understudied in Latin America. This study represents a decade-long effort to characterize the EGFR mutational landscape in a large Colombian cohort, addressing a critical regional data gap and providing a baseline for precision oncology. Methods: A retrospective observational study was conducted on 1,782 patients with NSCLC whose samples were centralized and analyzed at a national reference laboratory (UDHO) in Cali, Colombia (2014–2023). EGFR status was determined via real-time PCR (qPCR) using IVD/CE certified kits capable of detecting 42 mutations across exons 18–21. Testing utilized formalin-fixed paraffin-embedded (FFPE) tissue (n = 1,555) and plasma (n = 227, implemented in 2016). Strict quality protocols, including a minimum 10% neoplastic content and automated software analysis (LSR), ensured technical reproducibility. Results: The cohort showed a balanced sex distribution (50.5% female, 49.5% male) with ages ranging from 16 to 95 years. A total of 474 mutations were identified. Mutational prevalence was significantly higher in plasma (42%) compared to FFPE tissue (28%). Key findings include: Predominant Mutations: Exon 19 deletions (51.9%–60.8%) and L858R (19.9%–31.8%) were the most frequent. Resistance Profile: Identification of T790M co-mutations, most notably Exon 19 del + T790M (4.5% female; 6% male). Healthcare Barrier: 92.9% of studies were industry-sponsored, with only 7.1% covered by public health entities. The invalid result rate remained low, reflecting high pre-analytical standards. Conclusions: This longitudinal study—one of the most robust in the Andean region—confirms a high prevalence of actionable EGFR mutations in Colombian NSCLC patients. The data underscore that liquid biopsy is a vital diagnostic tool for increasing mutation detection rates in Latin America. These results highlight a critical "access gap," where precision diagnostics rely almost exclusively on pharmaceutical sponsorship, necessitating urgent public health policy shifts to ensure sustainable oncology care and health equity in the region.

A quiet crisis: Pancreatic cancer incidence, mortality, and DALYs in Latin America and the Caribbean (1980-2023).

e16395 Background: Pancreatic cancer remains a leading cause of cancer mortality globally, largely because it is frequently diagnosed at an advanced stage and responds poorly to available treatments. Recent data from high-income regions show a persistent upward trajectory in pancreatic cancer deaths, with Europe and the United States experiencing steady increases over the past two decades, including marked peaks during the COVID-19 pandemic. In contrast, Latin America’s pancreatic cancer burden has not been thoroughly analyzed over time, and its trends relative to those in Europe and the United States are not well characterized. Through this study, we aim to examine pancreatic cancer burden in Latin America and Caribbean from 1990 to 2023. Methods: Age-standardized death rates (ASDR), disability-adjusted life years (DALYs), Prevalence and Incidence of Pancreatic Cancers in Latin America were calculated from the Global Burden of Disease (GBD) Database 2023. Joinpoint Regression software was used for analysis. Prevalence and Incidence with 95 % uncertainty intervals and significant trends over time were identified. Statistical significance was set at a p-value &lt; 0.05. Results: Age-Standardized Death Rate (ASDRs) due to Pancreatic cancers in Latin America and Caribbean was reported to 4.56 in 1980, which rose to 5.58 in 2023, with an overall statistically significant increasing trend, dictated by AAPC of 0.51% (95% CI 0.32 to 0.70, p value &lt; 0.000001). Disability-adjusted life years (DALYs) due to Pancreatic cancers in Latin America and Caribbean has also risen from 112.58 in 1990 to 128.74 in 2023, with an uprising overall significant trend, reflected by AAPC of 0.42% (95% CI 0.26 to 0.59, p value &lt; 0.000001). Trend in Age-Standardized Incidence Rate (ASIRs) was also consistent with the overall upward trend, with reported AAPC of 0.57% (95% CI 0.40 to 0.74, p value &lt; 0.000001), with the mean ASIR of 4.70 in 1990, which increased to 5.63 in 2023. Conclusions: To sum up, the burden of pancreatic cancers has significantly risen in the past four decades, not only in Latin America and Caribbean but in the U.S and Europe too which highlights the need of early detection strategies, improved treatment protocols, and targeted preventive measures. These trends also emphasize the necessity for coordinated public health initiatives and enhanced cancer surveillance to address disparities and improve outcomes in high-risk populations.

Emergency department visits and hospitalizations in cancer survivors with disabilities: A national analysis.

1643 Background: One in four Americans has a disability. Adults with disabilities are known to have a higher cancer burden than the general U.S. population, but the healthcare utilization patterns and needs of this population remain understudied. We examined factors associated with emergency department (ED) visits and hospitalizations among cancer survivors, with a focus on disability status. Methods: We used National Health Interview Survey (NHIS) data from 2022-2024. Adults aged 18+ years who self-reported a diagnosis of breast, prostate, or colon cancer were included. Our key explanatory variable was disability status, defined by receipt of Supplemental Security Income or Social Security Disability Insurance, or a positive designation using the Washington Group Short Set Composite Disability Indicator. The primary outcomes were ED visits and hospitalization in the past 12 months. Logistic regression models adjusted for demographics and health status (e.g., body mass index, self-rated health, and smoking status). All analyses incorporate NHIS survey weights to account for the complex survey design. Results: Our sample included 4,179 NHIS respondents with breast, prostate, or colorectal cancer; 999 (23.9%) had a disability. Cancer survivors with disabilities were more likely to have less than a high school education (19.7% vs 9.2%), be enrolled in Medicaid (6.0 vs 2.7%) or Medicare (49% vs 44.8%), and report poor health status (22.3% vs 3.6%) compared to those without disabilities. Compared to cancer survivors without disability, those with disability had higher odds of ED visits (aOR 1.59 [95% CI 1.27-1.99], p&lt;0.001) and hospitalizations (aOR 1.70 [95% CI 1.30-2.22], p&lt;0.001). Other factors associated with increased odds of ED visits in cancer survivors were region (Ref=Northeast, South: aOR 1.33 [95% CI 1.01-1.77], p=0.046; West: aOR 1.46 [95% CI 1.09-1.98], p=0.01), Medicaid insurance (Ref=no insurance, aOR 1.93 [95% CI 1.01-3.69], p=0.046), and poor self-rated health (Ref=excellent, aOR 6.69 [95% CI 4.05-11.07], p&lt;0.001). Factors associated with increased odds of hospitalizations in cancer survivors were Medicare (Ref=no insurance, aOR 2.18 [95% CI 1.21-3.92], p=0.01), private insurance (Ref=no insurance, aOR 1.83 [95% CI 1.02-3.26], p=0.04), multiple insurance (Ref=no insurance, aOR 2.07 [95% CI 1.15-3.74], p=0.02), and poor self-rated health (Ref=excellent, aOR 6.96 [95% CI 3.82-12.70], p&lt;0.001). Conclusions: We observed an independent association between disability and ED visits and hospitalizations among cancer survivors in a national, population-based dataset. Geographic region, insurance, and poor health perception were additional risk factors for acute care utilization in cancer survivors. Our findings highlight the need for targeted interventions to improve ambulatory care access and reduce preventable acute care utilization in this vulnerable population.

Impact of protein–energy malnutrition on outcomes of metastatic triple-negative breast cancer patients receiving chemotherapy: A real-world analysis.

1135 Background: Protein–energy malnutrition (PEM) is common in patients with advanced cancer and is associated with increased toxicity, decreased treatment tolerance, and worse survival across malignancies. Data specific to metastatic triple-negative breast cancer (mTNBC), a biologically aggressive subtype, remain scarce. We evaluated the impact of PEM on outcomes in mTNBC patients receiving chemotherapy. Methods: We conducted a retrospective cohort study using de-identified data from TriNetX, a global federated health research network. Females with mTNBC on chemotherapy (paclitaxel, doxorubicin, capecitabine, eribulin, vinolrebine) were identified. PEM was defined using ICD-10 codes along with secondary definitions like BMI (&lt;20). The primary endpoint was overall survival (OS), estimated using the Kaplan-Meier method. Propensity matching was used to adjust for age, race and comorbidities. Two sided p≤0.05 was used to determine statistical significance. Results: A total of 1,644 patients with mTNBC were identified, of whom 761(46.3%) patients had PEM. The mean age was higher in the PEM group compared to the non-PEM group (64.5 vs 63 years, p &lt;0.05). African American patients were more likely to have PEM (37.0% vs 31.4%, p =0.02). After propensity score matching, 595 patients were included in each cohort for analysis. Patients with PEM had significantly worse 1-year OS compared to non-PEM group (65.7% vs 70.8%; HR 0.76, 95% CI 0.62–0.94, p &lt;0.05). At 2 years, survival remained numerically lower in the PEM group (56.2% vs 57.8%; HR 0.92, 95% CI 0.76–1.12), but the difference was not statistically significant. Conclusions: In this large real-world cohort of mTNBC, PEM was independently associated with worse 1-year overall survival. These findings underscore the prognostic significance of nutritional status in mTNBC and support routine nutritional assessment and early supportive interventions to improve outcomes in this high-risk population. Overall survival (OS) outcomes in matched mTNBC cohorts. Overall Survival PEM Group (n=595) Non-PEM Group (n=595) Hazard Ratio (95% CI) P-value 1-Year OS 65.7% 70.8% 0.76 (0.62–0.94) &lt;0.05 2-Year OS 56.2% 57.8% 0.92 (0.76–1.12) 0.41