Real-world Outcomes Research Articles

High density mapping accuracy and efficiency in atrial fibrillation: real-world outcomes from the SECURE registry

Abstract Background/Introduction A high-density (HD) mapping catheter is valuable for validating pulmonary vein isolation (PVI) and analysing arrhythmic substrates of the left atrium (LA) during atrial fibrillation (AF) ablation. Multiple HD mapping catheters are available for use in clinical practice. A novel octa-spline mapping catheter with a close internal unipolar reference electrode is now available and may improve mapping efficiencies and image resolutions (Figure). Purpose This study aims to report real-world experiences with different commercially available HD mapping catheters in AF ablation and compare mapping performance. Methods SECURE is an ongoing observational, prospective, post-marketing study collecting real-world data on ablation procedures performed per standard-of-care. At the time of data extraction (Nov. 2023), 16 sites across 8 countries had enrolled 2,366 patients (pts), with 12-month follow-up data available for 828 pts. The current analysis, which included consecutive pts undergoing AF ablation, evaluated mapping efficiency and procedural outcomes with 3 HD mapping catheters: circular catheter (CC), penta-spline catheter (PSC), and octa-spline catheter (OSC). Mapping data were analysed with a cloud-based data management and artificial intelligence-powered algorithm. Results Overall, 859 pts with AF (paroxysmal AF [PAF], n=465; persistent AF [PsAF], n=240; long-standing PsAF [LS PsAF], n=154) were included in this analysis. The CC, PSC, and OSC were used in 428, 210, and 221 pts, respectively. Procedures using the OSC had a significantly higher mean mapping area (31,989.9 mm2) than those performed with the CC (23,152.2 mm2; P<0.0001) and PSC (29,804.6 mm2; P=0.0027), as well as a >3-fold higher mean mapping rate (138.4 vs 20.8 and 43.4 points/min, respectively; both P<0.0001). The higher number of mapping points translated to a higher mean mapping density (OSC, 0.34 vs CC, 0.05 and PSC, 0.07 points/mm2; both P<0.0001), with more uniform point distribution and less interpolation. With the CC, PSC, and OSC, respectively, total mean procedure times (incl PVI + other targets) were 118.0, 118.7, and 165.1 min, (P<0.0001 for OSC vs. both CC and PSC) and mean pre-ablation mapping times were 25.2, 25.0, and 21.5 min (P<0.0004 for OSC vs. both CC and PSC). The improved mapping quality and efficiency with the OSC allowed to include specific ablation targets beyond PVI. Fewer PVI-only procedures were performed with the OSC (29.4%) versus the CC (62.1%) and PSC (54.8%), while ablation of the PVI+ other targets was more common with the OSC versus the CC and PSC, including the cavotricuspid isthmus (37.1% vs 17.3% and 16.7%), LA roof (42.5% vs 13.1% and 21.4%), and LA posterior wall (21.7% vs 10.5% and 16.2%). Results were overall consistent per AF type (Table). Conclusions By providing more accurate mapping, the OSC allows for improved analysis of the arrhythmic substrate, which may improve ablation outcomes for pts with PAF and PsAF.Figure 1

Efficacy and safety of catheter ablation for idiopathic premature ventricular contraction in Japan: from the nationwide Japan Catheter Ablation Registry

Abstract Introduction Catheter ablation (CA) is a viable approach for managing frequent idiopathic premature ventricular contractions (PVCs) associated with PVC-related cardiomyopathy. However, the real-world outcomes and appropriate indications for CA need further clarification. Methods This is the first nationwide analysis focusing on the efficacy and safety of CA of idiopathic PVCs. We analyzed 6,751 patients (age 58 [45-70], 3,265 males [48.4%]) who underwent their first CA for idiopathic PVCs with a single origin (3,849 right ventricular [RV] outflow tract [OT], 614 other RV, 1,517 in left ventricular [LV]-OT, and 771 in other LV), based on the Japanese Catheter Ablation Registry between August 2017 and December 2020. Results Success at discharge (SAD) was achieved in 5,276 (78.1%) patients, while 238 patients experienced recurrence before discharge (4.3% of those with acute success). SAD was achieved in 3,236/3,849 (84.1%) RVOT, 379/614 (61.7%) other RV, 1,145/1,517 (75.5%) LVOT, and 516/771 (66.9%) other LV patients (P <0.001). Age <50 and females were independent predictors for SAD. Conversely, obesity, origins other than RVOT, and low-volume facilities were independently inversely related to SAD. 171 (2.5%) acute complications, including 125 cardiac tamponades (CTs) (1.9%), were reported. Age ≥60 and females were independent predictors for both total complications and CTs. Remarkably, females aged ≥80 with RVOT origins exhibited a 10.3% rate of CTs. Conclusion Female patients aged <50 with OT-PVC without obesity, demonstrated favorable efficacy. However, non-OT PVCs were independently inversely related to SAD. Special attention should be given to females aged ≥60 with RVOT origins.

IRight4Me: individualisation of P2Y12 inihibitors in the realworld practice - an interim report

Abstract Background The uptake of CYP2C19 testing has been limited, as clinicians opined majority of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI) should receive Ticagrelor per international guidelines. Remaining minority with high bleeding risk (HBR) would be on Clopidogrel from the outset. We set out to study how clinicians’ knowledge of CYP2C19 phenotype affects choice of P2Y12 inhibitors, and thus real-world clinical outcomes for ACS patients. We report the interim findings of bleeding at 6 months in the Ticagrelor-loaded subgroup. Methods Patients eligible for escalation or de-escalation were recruited into the study and tested for CYP2C19 polymorphism. CYP2C19 phenotype results and recommendations were revealed to outpatient clinicians, giving them the choice to keep or switch P2Y12 inhibitors. Bleeding outcomes were prospectively tracked and adjudicated by independent study team members. Results A total of 740 patients who have completed 6 months from index admission for ACS were used for this analysis. Overall adjudicated MACCE and bleeding rates were 3.46% (n = 27) and 12.7% (n=95) respectively. CYP2C19 Non-LoF (Loss-of-Function) patients who were de-escalated to Clopidogrel were least likely to bleed (Fig 1). Ticagrelor-only patients experienced almost twice the risk of bleeding than those who were de-escalated to Clopidogrel, regardless of phenotype status (15.1% vs 7.8%, Cox HR, p = 0.042). High bleeding risk (HBR) factors did not explain for differences in bleeding. The non-LoF patients on Ticagrelor (n = 173) experienced more than 2-fold risk of bleeding compared to those de-escalated to Clopidogrel (n = 71), adjusted HR 0.389, p = 0.059. MACCE rates were similar between these two groups at 2.41% for Non-LoF continued on Ticagrelor (n = 164) and 2.44% for Non-LoF switched to Clopidogrel (n = 81) respectively. Conclusion Our interim analysis shows that Ticagrelor is associated with significantly higher rates of bleeding which could be mitigated by de-escalation to Clopidogrel. Non-LoF patients who have been de-escalated to Clopidogrel could be at much lower risk of bleeding, without losing out on MACCE outcomes. CYP2C19 phenotype status has the potential to add more precision to decision-making. We expect to report final results of 1000 patients at the end of 12 months to fully assess the impact of phenotype-guided de-escalation on bleeding and MACCE.

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Trends in intracardiac thrombus formation in myocardial infarction patients after PCI: a nationwide analysis

Abstract Background Percutaneous coronary interventions (PCI) have become a crucial therapeutic option for myocardial infarction (MI) patients. However, the clinical outcomes and complications associated with PCI, especially in relation to intracardiac thrombus, remain a subject of concern. Purpose We aimed to examine the real-world clinical outcomes and temporal trends of in-hospital mortality and intracardiac thrombus among myocardial infarction patients treated with PCI between 2017 and 2020. Methods The National Inpatient Sample was queried from 2017 to 2020 to identify all adults with myocardial infarction (ST elevation and Non-ST elevation MI) who underwent PCI using the International Classification of Diseases, 10th Revision codes. The Cochran-Armitage test assessed the linear trend of in-hospital intracardiac thrombus and mortality. Multivariable regression analysis was conducted to assess the association of PCI with in-hospital mortality and intracardiac thrombus. The Charlson comorbidity index was used to adjust for confounders. Results are represented as adjusted odds ratios (ORs) with their respective 95% confidence intervals (CIs). Results Of the 1,394,650 patients who underwent PCI, 8,080 (0.58%) experienced intracardiac thrombus, with a mean age of 62, predominantly male (76%). Despite decreasing rates of PCI noted over this 4-year period (Figure 1). There was an upward trend in in-hospital intracardiac thrombus revealed over a 4-year period (trend: 0.54%, p < 0.001). PCI was associated with a yearly increase in intracardiac thrombus in 2018 in 0.54% of patients (OR = 1.36, 95% CI 1.2 to 1.6, p < 0.001). In 2019, 0.56% of patients experienced intracardiac thrombus (OR = 1.4, 95% CI 1.2 to 1.6, p = 0.001); in 2020, 0.72% of patients (OR = 1.8, 95% CI 1.6 to 2.1, p = 0.008), compared to 2017 (0.4%). Mortality rates for PCI and ICT patients were 6% in 2017 (OR 2.2, p < 0.001, 95% CI 1.4-3.2), decreased to 5% in 2018 (OR 1.8, p < 0.004, 95% CI 1.2-2.6) and 4.7% in 2019 (OR 1.6, p < 0.01, 95% CI 1.1-2.4), then rose to 6.6% in 2020 (OR 2, 95% CI 1.4-2.8) (Table 1). Overall, in-hospital mortality was 5.6% (OR = 1.6, 95% CI 1.3 to 1.9, p < 0.001) among patients who had intracardiac thrombus related to PCI. Conclusions Our findings indicate a significant increase in intracardiac thrombus rates among MI patients treated with PCI from 2017 to 2020, accompanied by a considerable risk of in-hospital mortality. These outcomes underscore the critical need for vigilant monitoring and enhanced management approaches in this patient demographic.Figure 1Table 1

Comparing treatment strategies for heart failure: a real-world analysis of adding ARNI or SGLT2i to older GDMT

Abstract Background Heart failure (HF) is a global burden with limited treatment options beyond established guideline-directed medical therapy (GDMT). Newer medications, like angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), show promise, but real-world evidence on their effectiveness compared to traditional GDMT is lacking. Objective This study assessed the real-world effectiveness of adding ARNIs and SGLT2i to existing GDMT regimens for various HF types using network meta-analysis (NMA). Methods We analyzed data from observational studies, evaluating the impact of different treatment combinations on all-cause mortality (ACM) and heart failure hospitalization (HFH). Results Adding ARNIs to GDMT significantly reduced ACM compared to older regimens (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.42-0.84), representing a 41% decrease in mortality risk. SGLT2i+2GDMT demonstrated the most significant HFH reduction (HR 0.16, 95% CI 0.06-0.47), translating to an 84% reduction in hospitalization risk. Conclusion Incorporating ARNIs or SGLT2i into existing GDMT regimens improves real-world outcomes for HF patients, supporting current guideline recommendations. Personalized treatment plans considering individual needs and preferences are crucial for optimal patient care.Network map of All-cause mortalityRelative treatment effects for ACM

Real-World and Patient-Reported Outcomes of Dupilumab and Other Biological Drugs for Chronic Obstructive Pulmonary Disease—A Systematic Review

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three “real-world” case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients’ self-perceived drug effects, and none evaluated patients’ perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients’ experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials.

Early outcomes of robotic versus video-thoracoscopic anatomical segmentectomy: a propensity score-matched real-world study.

Minimally invasive anatomic segmentectomy for the resection of pulmonary nodules has significantly increased in the last years. Nevertheless, there is limited evidence on the safety and feasibility of robotic segmentectomy compared to video-assisted thoracic surgery. This study aimed to compare the real-world early outcomes of robotic and video-thoracoscopic in anatomic segmentectomy. Single centre cohort study including all consecutive patients undergoing segmentectomy by either robotic or video-thoracoscopic from June 2018 to November 2023. Propensity score case matching analysis generated two matched groups undergoing robotic or video-thoracoscopic segmentectomy. Short-term outcomes were analysed and compared between groups. 204 patients (75 robotic and 129 video-thoracoscopic patients) were included. After matching, 146 patients (73 cases in each group) were compared. One 30-day death was observed in the robotic group (P = 1). Two conversions to thoracotomy occurred in the robotic, and none in the video-thoracoscopic group (P = 0.5). Surgical time was longer in the robotic group (P = 0.091). There were no significant differences between robotic and video-thoracoscopic groups in postoperative complications (13.7% vs 15.1%, P = 1), cardiopulmonary complications (6.8% vs 6.8%, P = 1), major complications (4.1% vs 4.1%, P = 1), prolonged air leak (4.1% vs 5.5%, P = 1), arrythmia (1.4% vs 0%, P = 1) and reoperation (2.7% vs 2.7%, P = 1). Median length of stay was 3 days (IQR, 2-3 days) in the robotic group vs 3 days (IQR, 2.5-4 days) in the video-thoracoscopic group (P = 0.212). Robotic segmentectomy is a safe and feasible alternative to video-thoracoscopy, as no significant differences in early postoperative outcomes were found between the two techniques.

Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era

BackgroundTreatment for first-line (1L) metastatic non-small cell cancer (mNSCLC) changed with the introduction of immunotherapy. We describe treatment utilization and clinical outcomes in a real-world mNSCLC cohort in a 2.7-million-member state-mandated health provider.MethodsNewly diagnosed mNSCLC patients initiating systemic anti-cancer treatment (January 2017–December 2020) were identified from the National Cancer Registry. Real-world time on treatment (rwToT) was defined as the length of time between the first and last administration date of treatment. Real-world overall survival (rwOS) was estimated using Kaplan–Meier analysis. Outcomes were assessed at a minimum of 6 months’ follow-up (cutoff: 30 June 2021).ResultsAmong 843 patients, 85% had adenocarcinoma (NSQ) and 15% had squamous cell carcinoma (SQ) histology: of these, 43% and 26% were women, median age was 67 and 69 years, and 55% and 48% had 0–1 ECOG performance status, respectively (missing: 27% and 30%, respectively). Median follow-up for the entire cohort was 27.1 months (95% CI: 24.7–29.6). NSQ patients with no known EGFR/ALK/ROS1 aberrations received PD-1 inhibitor monotherapy (PDM) (N = 147) or combination (PDC) (N = 194) or platinum-based chemotherapy (PBC, N = 133). Median rwToT was 4.5 (95% CI: 3.5–7.6), 5.2 (95% CI: 4.6–7.6), and 2.3 (95% CI: 2.1–3.0) months, respectively; for the subgroup of patients with ECOG PS 0–1, rwToT was 9.4 (95% CI: 5.0–20.8), 7.1 (95% CI: 5.0–10.1), and 2.9 (95% CI: 2.2–4.1) months, respectively. Median rwOS from 1L was 12.5 (95% CI: 9.9–17.9), 14.8 (95% CI: 10.5–19.4), and 9.1 (95% CI: 7.1–11.5) months; for the subgroup of patients with ECOG PS 0–1, median rwOS was 25.1 [95% CI: 14.9–not reached (NR)], 17.6 (95% CI: 14.3–NR), and 11.3 (95% CI: 9.2–21.3) months, respectively. For ECOG PS 0–1 and PD-L1 ≥50% patients, median rwOS was 25.1 months (95% CI: 13.9–NR) and NR for PDM and PDC, respectively. For ECOG PS 0–1 and PD-L1 <50% patients, median rwOS was 14.3 (95% CI: 10.1–NR) and 11.2 (95% CI: 9.1–21.3) months for PDC and PBC, respectively.ConclusionOur real-world data support the benefit of single-agent PD-1 inhibitor monotherapy for patients with PD-L1 high expression or PD-1 inhibitor combination for all patients diagnosed with mNSCLC with no known EGFR/ALK/ROS1 aberrations, initiating 1L treatment.

Real-world clinical outcomes of tixagevimab/cilgavimab in the Omicron outbreak in China: baseline characteristics and interim analysis of the CLEAR study

PurposeThis study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022.MethodsThis observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis.ResultsAmong 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab.ConclusionAmong Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes.Trial registrationThe study was registered with clinicaltrial.gov (NCT05917951).

Optimizing Treatment Strategies for Egfr-Mutated Non-Small-Cell Lung Cancer Treated with Osimertinib: Real-World Outcomes and Insights

Background: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated superior efficacy over first-generation TKIs in the FLAURA trial, resulting in its approval as first-line therapy for metastatic non-small-cell lung cancer (NSCLC). However, the real-world application of these trial results requires an evaluation of sequential therapeutic strategies. Methods: This retrospective, non-interventional study utilized data from the Epidemiological Strategy and Medical Economics (ESME) platform, which includes information on patients treated for lung cancer since 2015. Out of 39,974 patients in the database, 624 patients with EGFR-mutant advanced NSCLC treated with osimertinib as first-line (L1, n = 198) or second-line (L2, n = 426) treatment after first- or second-generation TKIs (n = 1262) were identified. Patient demographics, disease characteristics, treatment strategies, and disease progression were examined. Survival analyses were performed using Kaplan–Meier estimates and Cox proportional-hazards models. Results: In the study population (n = 624), 73.4% were female, with a median age of 70 years (range 28–93). Brain metastases at the start of osimertinib treatment were observed in 282 patients. ECOG PS-2 was reported in 29.4% of patients. The T790M mutation in exon 20 was identified in 257/426 patients (60.3%) receiving osimertinib in L2. Median progression-free survival (PFS) was 12.4 months (95% CI [10.7–14.7]) for L1 and 7.4 months (95% CI [6.2–8.7]) for L2. Median overall survival (OS) from advanced diagnosis was 28.5 months (95% CI [26.3–38.7]) for osimertinib L1 and 29.9 months (95% CI [28.6–31.8]) for osimertinib L2 (HR = 0.93; 95% CI [0.75–1.16]; p = 0.50). For L1, median OS was 27.1 months (95% CI [22.0–30.2]) for patients with cerebral metastases and 38.7 months (95% CI [26.3–52.8]) for those without (HR = 0.73; 95% CI [0.48–1.11]; p = 0.15). Discussion: Patients in the real-world ESME database exhibited a poorer prognosis compared to those in the FLAURA trial. The presence of cerebral metastases at diagnosis worsens the prognosis.

Real world comparison of filgrastim to filgrastim-sndz in patients with chemotherapy-induced neutropenia.

There exists some apprehension by prescribers, healthcare providers, and other stakeholders regarding the real-world safety and effectiveness of biosimilars. While some of the apprehension is likely due to clinician knowledge gaps in the biosimilarity exercise, additional data (including those generated from the real-world) regarding safety and efficacy could reduce a clinician's perception of biosimilar uncertainty and can potentially increase biosimilar acceptance and uptake. The published literature is lacking regarding the real-world impact on healthcare costs and clinical outcomes when a single healthcare institution converts from filgrastim to filgrastim-sndz as its short-acting Granulocyte Colony Stimulating Factor (GCSF), especially within diverse populations and indications not explicitly studied through the registration trials. Specifically, both filgrastim and filgrastim-sndz possess FDA-approved indications within patients with hematologic malignancies receiving high-dose chemotherapy and in those undergoing bone marrow transplantation. As a biosimilar to filgrastim, the FDA did not require prospective, randomized controlled trials to obtain these indications for filgrastim-sndz. The purpose of this study is to describe real-world healthcare resource costs, utilization patterns, and clinical outcomes in patients with hematologic malignancies who received filgrastim-sndz or filgrastim to support neutrophil recovery following chemotherapy (i.e., induction or consolidation) or a bone marrow transplant (BMT) at Yale New Haven Hospital (YNHH). A total of 148 patients were identified and met the following criteria: at least 18 years old, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, absence of fever or infection, newly diagnosed acute myeloid leukemia or newly post-bone marrow transplant and received filgrastim-sndz (Zarxio®) or reference filgrastim (Neupogen®). Healthcare resource utilization outcomes were compared between biosimilar and reference filgrastim using descriptive statistics. There were no major differences between either cohort, including duration of hospitalization, the number of overall emergency room visits and additional hospital admissions with a primary diagnosis of febrile neutropenia or neutropenia within 30 days post-discharge from initial hospital admission, time to neutrophil recovery following GCSF support, and the incidence and duration of both fever and febrile neutropenia. The total cost based on treatment of all patients in each arm differed significantly with filgrastim-sndz being the most cost-effective choice. filgrastim-sndz significantly reduced healthcare utilization costs compared to reference filgrastim with similar effect on absolute neutrophil count, incidence of fever, and febrile neutropenia.

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

Abstract X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking. A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P<.001) and physical function (-14.3 ± 16.2, P=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

Real-World Outcomes with the KEYNOTE-522 Regimen in Early-Stage Triple-Negative Breast Cancer.

This study aimed to determine if the neoadjuvant (NAT) KEYNOTE-522 regimen was associated with higher rates of pathologic complete response (pCR), corresponding to higher rates of breast conservation therapy (BCT) in early-stage triple-negative breast cancer (TNBC) patients. Stage II-III TNBC patients diagnosed between 2019 and 2022 who underwent NAT were analyzed retrospectively. NAT with KEYNOTE-522 versus control NAT were compared for rates of BCT, axillary node dissection (ALND), pCR, and survival outcomes. The prevalence of immune-related adverse events (irAE) from chemoimmunotherapy was recorded. Of 240 patients identified: 86 received KEYNOTE-522 and 154 received control. The frequency of pCR was significantly higher in KEYNOTE versus the control cohort, 59.3% and 33.1%, respectively (p = 0.001). There was no significant difference in the rate of BCT between the control (33.1%) and the KEYNOTE-522 (32.1%) groups (p = 0.47). Rates of ALND were significantly lower with KEYNOTE-522 (25.6%) as compared with control (39.6%); p = 0.03. The rate of development of grade 2 or higher irAEs was 34.9%. At a median follow-up of 2.4 years, there was no difference in survival outcomes. BRCA1 patients had high rates of pCR regardless of treatment group, KEYNOTE-522: 80.0% (4/5) and control: 75% (9/12), (p = 1). This real-world evidence supports the use of the KEYNOTE-522 regimen in patients with early-stage TNBC given the higher pCR rate and corresponding decrease in the rate of ALND. The majority of patients in both NAT cohorts became BCT eligible, but the rate of BCT did not differ between the two groups.

Real-World Treatment Outcomes Associated with Early Versus Delayed Vedolizumab Initiation in Patients with Ulcerative Colitis

Abstract Background Patients with ulcerative colitis (UC) typically receive a targeted inflammatory bowel disease therapy after treatment with conventional therapies and after the development of significant morbidity. Evidence suggests that early biologic treatment after diagnosis could improve treatment response and prevent disease complications compared with delayed biologic treatment after conventional therapy. Methods RALEE was a retrospective study using claims data from IBM® MarketScan® Research Databases between January 1, 2016 and December 31, 2019. Adults with UC and at least one claim for vedolizumab were categorized into Early or Delayed Vedolizumab groups according to whether they had received vedolizumab within 30 days of diagnosis or after conventional therapy (5-aminosalicylates, corticosteroids, and immunomodulators), respectively. Treatment response was assessed at 2, 6, and 12 months after vedolizumab treatment initiation and was analyzed with logistic regression (bivariate). Results At 2 months, Delayed Vedolizumab was associated with significantly higher odds of nonresponse than Early Vedolizumab (odds ratio [OR], 2.509; 95% confidence interval [CI], 1.28–4.90). Delayed Vedolizumab was not significantly associated with odds of nonresponse at 6 months (OR, 1.173; 95% CI, 0.72–1.90) or at 12 months (OR, 0.872; 95% CI, 0.55–1.37). Mean total healthcare costs were similar in the Early Vedolizumab ($6492) and Delayed Vedolizumab ($5897) groups, although there were small differences in costs from different types of claims. Conclusions Patients who received vedolizumab early after UC diagnosis were less likely to experience nonresponse at 2 months and incurred similar healthcare costs at 12 months compared with patients who received delayed vedolizumab.

Real-world outcomes in patients with brain metastases secondary to HR+/HER2- MBC treated with abemaciclib and local intracranial therapy.

Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) MBC with brain metastases diagnosis before abemaciclib initiation. A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2- MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date). Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively. In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.

Genomic landscape of circulating tumor DNA and real-world outcomes in advanced endometrial cancer.

ctDNA is a novel technique extensively studied in solid tumors, although not currently well defined in endometrial cancer (EC). A de-identified retrospective analysis of 1988 patients with advanced/recurrent EC was performed. In addition, an analysis of a real-world evidence (RWE) cohort was completed (n=1266). Patients underwent ctDNA testing using Guardant360 during routine clinical care. The objective was to describe and assess molecular landscape using ctDNA. Among 1988 ctDNA samples, at least one somatic alteration was detected in 91.6% (n=1821). Most frequently altered genes were TP53 (64%), PIK3CA (29%), PTEN (25%), ARID1A (20%) and KRAS (14%). Overall, 18.5% had amplifications, with the majority identified in CCNE1 (40.9%), PIK3CA (22%) and EGFR (19.3%). From the RWE cohort, those with TP53 mutations had a worse overall survival (OS) vs those without TP53 mutations (p=0.02) and those with TP53 co-mutations had an inferior OS in comparison to TP53-mutated only (p=0.016). Amongst these, patients with a PIK3CA co-mutation (p=0.012) and CCNE1 amplification (p=0.01) had inferior OS compared to those with only TP53 mutations. 57 patients with newly diagnosed EC had at least 2 serial ctDNA samples showing evolution in detected variants compared to baseline samples, with TP53 being the most frequent change. This study is one of the largest cohorts of ctDNA currently reported in EC. The presence of TP53 mutation and other co-mutations detected by ctDNA have a negative effect on outcomes. This report suggests that ctDNA analysis is feasible and could become a useful biomarker for EC.

P4.07G.03 Real-World Clinical Outcomes and the Association Between EFS and OS in Early-Stage NSCLC Treated with Primary SBRT

P4.07G.03 Real-World Clinical Outcomes and the Association Between EFS and OS in Early-Stage NSCLC Treated with Primary SBRT

Real-World Clinical Outcomes of Treatment With Olaparib for BRCA1/2 Mutation-Positive Metastatic Breast Cancer in Japanese Patients

Real-World Clinical Outcomes of Treatment With Olaparib for BRCA1/2 Mutation-Positive Metastatic Breast Cancer in Japanese Patients

Perceptions of Anti-Black Bias in the Criminal Justice System Contribute to Pro-Black (Versus White) Bias in Criminal Justice Research

Black Americans experience more frequent guilty verdicts and harsher sentences in the criminal justice system. However, recent laboratory work often finds either trivial differences or a pro-Black bias where people provide more lenient verdicts for Black versus White defendants. Across five studies, we find a consistent pro-Black bias even after reducing social desirability concerns. Instead, the pro-Black bias results from a negative relationship between perceived anti-Black criminal justice bias and the Black suspect’s verdict. The current work shows the pro-Black bias as a consequence of the newly salient perception of racial bias in the criminal justice system. Consequently, as people’s perceptions of racial disparities in the criminal justice system increase, this in-lab effect may manifest in real-world criminal justice outcomes.