Real-world Clinical Outcomes Research Articles

Real-world clinical outcomes and rationale for initiating abatacept as a first-line biologic for patients with anticitrullinated protein antibody- and rheumatoid factor-positive rheumatoid arthritis

Aim: In rheumatoid arthritis (RA), seropositivity for both anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) is associated with disease severity and therapeutic response. Biologic (b) disease-modifying antirheumatic drugs (DMARDs) such as abatacept are recommended after inadequate response or contraindication to conventional synthetic DMARDs. This retrospective cohort study aimed to describe changes in Clinical Disease Activity Index (CDAI) measures over 12 months among patients with ACPA+ and RF+ RA with an inadequate response to methotrexate treated with abatacept as a first-line bDMARD. Patients & methods: Patient data were abstracted from medical records by treating rheumatologists. Analyses included McNemar tests for paired proportions or paired t -tests to assess longitudinal changes in CDAI scores, and Kaplan–Meier methods for time-to-event outcomes. Serious AEs and rationale for initiating treatment were recorded. Results: Overall, 296 patients were included. Mean CDAI scores improved (decreased) by 34.0, 61.0 and 74.0% (all p < 0.001) from baseline to 3–6 months, 6–12 months and ≥12 months after abatacept initiation, respectively. Of 279 patients not in CDAI low disease activity (LDA) or remission at baseline, 24.7% of patients achieved it within 6 months, 56.3% within 12 months and 71.0% at any point during follow-up after abatacept initiation. Median time to CDAI LDA/remission was 10.2 months. Serious AEs were reported in 2.4% of patients. Common reasons reported by rheumatologists for initiating abatacept were effectiveness/efficacy (52.7%), safety (31.4%) and patient preference (25.3%). Conclusion: In this analysis of patients with ACPA+ and RF+ RA treated with abatacept as a first-line bDMARD in a clinical practice setting, clinical outcomes and remission rates were improved at all time points, providing real-world evidence to further support the use of abatacept in this patient population.

Evolution of treatment strategies for solid tumors with RET rearrangement in China and real-world treatment status of Non-small Cell Lung Cancer (NSCLC)

ObjectiveThe present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population.MethodsThe study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE).ResultsA retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3–4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population.ConclusionThis study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Locally Advanced or Metastatic Urothelial Carcinoma by Eligibility for Maintenance Avelumab

Real-World Treatment Patterns and Clinical Outcomes in Patients With Locally Advanced or Metastatic Urothelial Carcinoma by Eligibility for Maintenance Avelumab

Real-World Clinical Outcomes of Neoadjuvant Platinum-Based Chemotherapy with Nivolumab in Non-Small Cell Lung Cancer.

Background: Lung cancer is among the most prevalent and serious forms of cancer, characterized by an allogenic phenotype that presents significant therapeutic challenges. Materials and Methods: We analyzed medical records from January 2022 to August 2023, focusing on individuals aged 18 and older diagnosed with resectable NSCLC who received neoadjuvant chemo-immunotherapy prior to surgical intervention. Results: The cohort comprised 56 patients, predominantly smokers (95%) and male (74%), with 80% presenting the disease at stage III. Of the participants, 44 underwent surgery, with 95% receiving lobar resection. Clinical assessments via PET-CT imaging revealed an 86% rate of response or disease stabilization, while pathological evaluations showed complete and major pathological responses in 61% of cases. Conclusions: This real-world data supports the safety and efficacy of incorporating immune checkpoint inhibitors in the neoadjuvant treatment of NSCLC, followed by surgical resection.

Molecular tumor board in patients with metastatic breast cancer.

Comprehensive genomic profiling is becoming increasingly important in the management of patients with metastatic breast cancer (mBC). Real-world clinical outcomes from applying molecular tumor boards (MTBs) recommendations in this context remain limited. Accordingly, we conducted a retrospective, single-institution analysis to evaluate the clinical impact of discussing patients affected by mBC at the MTB. Clinicogenomic data of patients affected by mBCs referred to the European Institute of Oncology MTB between August 2019 and December 2023 were reviewed. Genomic alterations were classified by ESCAT framework. Clinical outcomes of patients showing actionable alterations and receiving molecular-matched therapy (MMT) were compared to those receiving standard therapy (ST). Ninety-six patients were included. Following MTB discussion, genetic counseling was recommended in 27% (n = 26) of patients, while additional molecular analyses were requested in 25% (n = 24) cases. Fifty-six patients (58%) displayed at least one actionable alteration. For patients with available follow-up (n = 50), 32 (64%) received MMTs and 18 (36%) ST. No differences in real-world progression-free survival (rwPFS) (4.07 months [95% CI 2.14-8.28] vs. 3.12 months [95% CI 1.51-NE], P = 0.8) and 12-month overall survival (OS) (58% [95%CI 43-78] vs. 57% [95%CI 34-97), P = 0.9) were observed between the MMT- and ST-group. Level I ESCAT alterations yielded longer rwPFS (5.82 months [95% CI 3.12-8.41]) compared to ESCAT II (2.14 months [95%CI 1.61-NE]) and ESCAT III (2.10 months [95% CI 2.04-NE]; P = 0.03). Twenty-four percent of patients showed a PFS2/PFS1 ratio > 1.3 from MMT. Molecular tumor boards can provide additional treatment options for patients affected by mBC. Besides treatment recommendations, MTBs also have the utility to assess the validity of discussed genomic reports and to identify alterations worthy of genetic counseling.

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.

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 &amp;lt; 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 &amp;lt; 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 &amp;lt; 0.001, 95% CI 1.4-3.2), decreased to 5% in 2018 (OR 1.8, p &amp;lt; 0.004, 95% CI 1.2-2.6) and 4.7% in 2019 (OR 1.6, p &amp;lt; 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 &amp;lt; 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

Real-world clinical features and survival outcomes in diffuse large B-cell lymphoma patients with hepatitis B virus infection

ObjectiveHepatitis B virus (HBV) infection is associated with the incidence and prognosis of diffuse large B-cell lymphoma (DLBCL), and previous studies differ in terms of clinical characteristics and prognostic factors. In this study, we explored the clinical features and prognostic characteristics of real-world DLBCL patients infected with HBV.MethodsPatients with pathologically diagnosed primary DLBCL at West China Hospital of Sichuan University were enrolled. Patients with follicular lymphoma-transformed DLBCL, primary central nervous system DLBCL, and hepatitis C virus, hepatitis E virus, human immunodeficiency virus, or syphilis infections were excluded. Ultimately, a total of 941 patients were included in this study. All patients included in the study underwent HBV serum marker testing before treatment. The demographic features, clinical characteristics and treatments of patients with different HBV infection states were collected and analyzed comprehensively to identify prognostic factors for OS and PFS.ResultsStatistical analysis of the data revealed that hepatitis B surface antigen positive (HBsAg +) DLBCL patients were younger and more likely to present with advanced disease, germinal center B cell-like subtype, B symptoms and splenic involvement. There were no significant differences in OS or PFS among patients with different HBV infection statuses (χ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upchi$$\\end{document}2 = 0.139, P = 0.933; χ2 = 0.787, P = 0.675); R-CHOP/R-CHOP-like regimens improved prognosis in HBsAg + DLBCL patients (OS: χ2 = 7.679, P = 0.006; PFS: χ2 = 9.042, P = 0.003); antiviral prophylaxis for HBsAg + DLBCL patients improved OS and PFS (HR: 0.336, P = 0.012, 95% CI [0.143, 0.788]; HR: 0.397, P = 0.032, 95% CI [0.171, 0.925]), with tenofovir treatment being particularly effective (χ2 = 4.644, P = 0.031; χ2 = 4.554, P = 0.033).ConclusionsHBsAg + DLBCL patients have unique clinical characteristics, and the use of CD20 monoclonal antibody based regimens significantly improves the outcome and prognosis of patients with HBsAg + DLBCL. Anti-HBV therapy, especially tenofovir, improves the prognosis of DLBCL patients with HBV presenting infection. Timely and sustained antiviral prophylaxis should be the standard strategy for treating DLBCL patients with HBV infection to optimize the efficacy of chemotherapy and immunotherapy.

Real-world clinical and economic outcomes from rapid start antiretroviral therapy in HIV: systematic review and meta-analysis.

We aimed to synthesize clinical and economic outcomes of rapid start versus non-rapid antiretroviral therapy (ART) in people with HIV (PWH) in real-world settings. A search was conducted in PubMed, Embase, Web of Science, and ProQuest from January 2017 to January 2023, supplementing a previous search by Ford et.al, 2018. Observational studies investigating clinical or economic outcomes of rapid start ART versus non-rapid ART in PWH were included. Clinical outcomes were mortality, loss-to-follow-up (LTFU), and viral suppression. Economic outcomes were Incremental cost-effectiveness ratio (ICER) values and per patient per month (PPPM) costs. Meta-analyses using random-effects models were performed for clinical outcomes, while qualitative syntheses were conducted for economic outcomes. The quality of clinical and economic studies was assessed. Sixty-two studies were included. The pooled adjusted risk ratio (aRR) for mortality demonstrated a significant reduction in risk of mortality among participants who received rapid start ART compared to non-rapid ART (0.80, 95%CI, 0.65-0.98). For LTFU at 6 and 12 months, the pooled aRR showed increased LTFU for rapid start ART (1.33, 95%CI, 1.15-1.55 and 1.18, 95%CI, 0.74-1.89 respectively). All cost-effectiveness studies reported cost-saving or cost-effective findings. The PPPM costs of rapid start ART across the first 36 months of treatment were consistently lower than non-rapid ART. Rapid ART is associated with reduced mortality and is cost-effective compared to non-rapid ART in real-world settings. Clinicians and policymakers should consider these findings to facilitate rapid start of ART in PWH. Further research on LTFU in PWH is needed.

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

Treatment 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. Newly 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). Among 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. Our 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).

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.

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.

Background Olaparib is effective in the treatment of metastatic breast cancer (MBC) patients, mainly confirmed by deleterious germline BRCA mutations. However, real-world data are scarce. Methodology A total of 10 cases from our institute and 17 cases from the relevant Japanese literature were reviewed. All 27 patients had MBC with confirmed deleterious germline BRCA mutations. Tumor reduction, response duration, disease-free interval (DFI), overall survival (OS), and safety were assessed. Additionally, exploratory research was conducted on the characteristics of a subgroup of patients who had a long-term response to olaparib. Results In the 10 cases from two Juntendo hospitals who received olaparib from July 2018 to December 2021, the median age was 48 years (range = 37-63 years). The same numbers of BRCA1 and BRCA2 mutations and the same ratios of luminal and triple negative (TN) breast cancer cases were observed. The metastatic sites, mainly visceral, included the lungs (n = 4), liver (n = 5), and bone (n = 6). The median duration of drug use was four months (range = 1-36 months). The median number of treatment regimens from metastasis to olaparib administration was 2.0 (range = 1-9 regimens). The median DFI was 21 months (range = 0-106 months). The median OS was not reached (range = 16-191 months). In the subgroup analysis of six cases in which olaparib was effective for four months or more, there was a case where DFI was longer than 100 months. Treatment-related toxicities (TRTs) included neutropenia (n = 5; 50%), anemia (n = 4; 40%), thrombocytopenia (n = 2; 20%), nausea (n = 1; 10%), and fatigue (n = 1; 10%). CTCAE (version 5.0) grade ≥3 TRTs included anemia (n = 1; 10%) and neutropenia (n = 5; 50%). On the other hand, neutropenia was previously said to be as low as 27.3%, lower than anemia (40.0%), in a population including various races. We additionally examined another 17 cases from the Japanese literature. Conclusions To our knowledge, this study reports the first real-world data of Japanese patients with MBC and confirmed deleterious germline BRCA mutations. Our data showed that olaparib is effective in the real world. The incidence of neutropenia seemed higher in Japanese patients.

Early real-world experience with intravitreal Faricimab for neovascular AMD: FAN study

PurposeThis study presents real-world experiences and clinical outcomes of patients who switched to faricimab after prior treatment with other anti-vascular endothelial growth factor medication for patients with neovascular age-related macular degeneration (nAMD) in 2022. DesignWe evaluated all consecutive patients that received an intravitreal injection (IVI) with faricimab for nAMD and had complete follow-up visits after at least three IVI. MethodsFunctional and structural parameters including best-corrected visual acuity (BCVA, logMAR), foveal centre point (FCP, µm), central subfield retinal thickness (CSRT, µm) and macular volume (mm3) were evaluated after three (n = 71) and five (n = 57) faricimab injections with complete follow-up visits. ResultsWe included 71 eyes of 63 patients. Mean BCVA at baseline was 0.49 logMAR (0 – 1.6) and did not change significantly after five faricimab injections (p = 0.33). Significant reductions were seen for FCP, CSRT and macular volume after the first five consecutive injections when compared to baseline (p < 0.0001 respectively). FCP was 388.35 µm (173–924 µm) at baseline and decreased to 279.16 µm (97 – 667) at visit 5. CSRT was 370.68 µm (202 – 1074) and decreased to 307.75 µm (168 – 590) at visit 5. Macular volume was reduced from 2.59 mm3 (1.83 – 4.90) to 2.31 mm3 (1.80 – 3.19) at visit 5. Intraocular inflammation was observed in one eye showing anterior chamber cells that resolved with topical corticosteroid treatment. ConclusionsThe results of the FAN (FAricimab for Neovascular AMD) study indicate that faricimab improves structural outcomes in patients with recalcitrant fluid due to nAMD with no major complications observed.

Infrarenal Aortic Treatment With AFX2 Endograft: Results From a Multicentric, International, Non-Randomized, Prospective Registry-the AFX2-LIVE Study.

To confirm real-world clinical practice results reported with anatomically fixed bifurcated endograft, a physician-initiated study was designed-AFX2-LIVE registry. From November 2019 to August 2021, investigators enrolled all consecutive patients treated with AFX2 (Endologix Inc., Irvine, CA, USA) endograft. Patients with abdominal aortic aneurysms (AAAs), penetrating aortic ulcers (PAU), and isolated infrarenal aortic dissections were included. Clinical and anatomical data, including baseline, intraoperative, and in-hospital details, as well as follow-up data, were collected in an anonymized prospectively compiled database. The primary endpoint of this study was to evaluate the technical and clinical success of endovascular aortic repair (EVAR) using AFX2 endograft. A total of 535 patients were enrolled from 43 Italian and Spanish centers and analyzed according to the protocol. Four hundred eighty-nine patients were male (91.4%), with a mean age of 75±8.92 years (range 52-94). Four hundred sixty-six patients (87.1%) were treated for AAA, 49 (9.3%) for PAU, and 20 (3.6%) for isolated abdominal aortic dissection. A proximal extension was needed in 48% of the cases. Assisted technical success was achieved in all but one patient (99.8%). At 30 days follow-up, no AAA-related deaths were recorded, and nine patients (1.6%) required reintervention. At a mean follow-up period of 15.22±13.65 (range 1-53) months, data were available for 479 patients (89.5%). Clinical success was achieved in 98.2% (95% confidence interval [CI]: 96.4-99.1) at 3 months, 93.9% (95% CI: 90.1-96.1) at 1 year, and 74.1% (95% CI: 62.8-82.4) at 4 years follow-up. The estimated freedom from all-cause mortality was 97.7%, 93.4%, 81.6%, 77.5%, and 70.9%, and freedom from AAA-related mortality was 100%, 99.6%, 99.6%, 99.6%, and 97.3% at 3, 12, 24, 36, and 48 months, respectively. Twenty reinterventions (3.7%) were required in 19 patients, of which 3 late open conversions (0.6%) were performed, and 2 AAA-related deaths were observed. This study demonstrated excellent clinical and technical success rates of EVAR with anatomically fixed endografts, providing valuable insights into real-world clinical outcomes. The AFX2-LIVE study could have a significant impact by providing robust evidence supporting the effectiveness and safety of EVAR using bifurcated endografts with anatomical fixation in real-world clinical practice, ultimately leading to improved outcomes and enhanced patient care in the management of abdominal aortic pathologies.

Real world clinical outcomes from targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer: data from a large cohort at a national cancer institute.

Randomised evidence supports the use of partial breast irradiation (PBI) with targeted intraoperative radiotherapy (TARGIT-IORT) for early stage breast cancer, but prospective data from real-world adoption of this technique is also important. The aim of this study was to determine if the outcome reported in TARGIT-A trial could be replicated in large cohort of early stage breast cancer treated with TARGIT-IORT. This prospective observational study analysed all patients treated with TARGIT-IORT between 2004 and 2021 in a single national cancer institute. TARGIT-IORT during lumpectomy was performed according to the risk-adapted TARGIT-A protocol using the Intrabeam® device. We analysed the completeness of follow up, 5-year in-breast-tumour-recurrence (IBTR), long term local recurrence free survival, distant disease-free survival, overall survival and breast-cancer-related survival, using the Kaplan-Meier method. A covariate analysis was performed to investigate risk factors for IBTR. We also analysed high grade toxicity events. The study included 814 patients and the a median follow up was 72 months. The majority of patients (60.3%) received TARGIT-IORT as PBI modality ("exclusive IORT" group); 39.7% received additional EBRT. There was no significant difference between the 5 years IBTR for the whole study population and the "exclusive IORT" cohort (1.6% (95%CI=1.1-2.1%) and 2.5% (95%CI=1.7%-3.3%) respectively). 5 years overall survival and tumour related survival were >95%. In 21% of patients with recurrence, breast was preserved. Radiotherapy toxicity (CTCAE Grade>2) was very rare (0.9%). This large single institute study found that breast cancer control and survival outcomes with TARGIT-IORT were consistent with TARGIT-A trial results. This "real world" experience confirmed that the randomised evidence showing the value of TARGIT-IORT as partial breast irradiation modality that can be replicated in routine clinical practice.

Real-World Clinical Outcomes With Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.

Sacituzumab govitecan (SG) is approved for the treatment of metastatic triple-negative breast cancer (mTNBC). We report the real-world clinical effectiveness and toxicity data of SG in patients with mTNBC. A multi-institution retrospective study of patients with mTNBC treated with SG from January 2021 to May 2023 was conducted. Demographic and clinicopathologic variables were collected. Univariate and multivariate Cox regression models were used for survival analysis. A total of 115 patients were included. The median age at SG initiation was 60 years (range, 31-85). All patients were female; 73 (63.5%) were White and 31 (27.0%) were Black. The median number of previous therapies in the metastatic setting was two (range, 0-8). Sixty-one (56.0%) patients had primary refractory disease. Median relative dose intensity was 92% (range, 33%-100%). Grade 3 or higher adverse events (AEs) were seen in 50.9% of patients, which included neutropenia (35.7%), anemia (27.0%), vomiting (16.5%), fatigue (8.7%), and diarrhea (7.0%). Dose reductions and treatment discontinuation due to AEs were required in 51.3% and 13.2%, respectively. The objective response rate (ORR) was 27.8%. Median overall survival was 9.6 months (95% CI, 7.8 to 12.9) and median progression-free survival (PFS) was 4.8 months (95% CI, 3.6 to 5.9). In patients with human epidermal growth factor receptor 2 (HER2)-low mTNBC who received trastuzumab deruxtecan (T-DXd) after SG, the ORR to T-DXd was 34.8% and median PFS was 7 months (95% CI, 4.6 to 10.1). In a real-world cohort of heavily pretreated patients with mTNBC, SG retains its clinical activity. In a subgroup with HER2-low disease, T-DXd continues to demonstrate promising clinical activity after SG, supporting the use of sequential antibody-drug conjugates in this population.

Real-world clinical outcomes among patients with non-squamous advanced non-small cell lung cancer (aNSCLC) treated with docetaxel-based regimens post initial standard of care (SOC) in the United States.

392 Background: Immunotherapy (IO) or targeted therapy used separately or in combination with platinum-based chemotherapy (PBC) are SOC among treatment naïve aNSCLC patients. After progression on SOC, patients have limited treatment options. Previous US-based real-world studies have shown docetaxel ± ramucirumab as the most used line of treatment (LOT) post-SOC. This study sought to assess clinical outcomes associated with docetaxel+ramucirumab (DTX-R) or docetaxel monotherapy (DTX) received post SOC among patients with non-squamous aNSCLC independent of genomic alteration status. Methods: This retrospective study, using electronic medical record data from the ConcertAI Patient360 NSCLC data product (01/2015–09/2022), included adult patients (≥18 years) with stage IIIB-IV non-squamous aNSCLC who received docetaxel-based regimens (DTX-R or DTX) as subsequent LOT (index LOT) after discontinuation of the prior qualifying SOC LOT (IO + PBC or targeted therapy + PBC). Kaplan-Meier analysis was used to estimate median time to discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) on docetaxel-based index regimens. Results: Out of 656 non-squamous aNSCLC patients which discontinued prior SOC therapy, 165 (25.2%) received a docetaxel-based regimen (n = 96 [DTX-R]; 69 [DTX]) which was the most commonly received index regimen. Other patients received a variety of other treatments, most commonly, pembrolizumab monotherapy (11.4%), pemetrexed + pembrolizumab (8.4%), pemetrexed monotherapy (4.4%), carboplatin + pemetrexed (4.1%), and osimertinib (3.8%). Among patients with index DTX-R and DTX, median age was 66 and 65 years; 36.5% and 60.9% were female; 74.0% and 63.8% were White; 86.5% and 75.4% received care in community setting; 15.1% and 31.8% had brain metastasis; 63.6% and 65.2% had ECOG 0-1; 1 and 2 median prior LOT; and median follow-up from index was 10 and 11 months, respectively. Median TTD, TTNT, rwPFS, and rwOS for docetaxel-based regimens are reported in the table. Conclusions: Docetaxel ± ramucirumab is the most used regimen in a fragmented treatment landscape post SOC therapy among patients with non-squamous aNSCLC. Observed rwOS, rwPFS, and treatment durations on docetaxel-based regimens in this real-world setting suggested the limited clinical benefit associated with these therapies. Overall, there is a need for more effective treatment options post SOC therapies. Real-world outcomes for DTX-R and DTX treated patients post SOC. Outcome, months (median, 95% CI) Docetaxel+Ramucirumab Docetaxel Monotherapy rwOS 6.37 (4.4, 9.3) 4.73 (2.3, 7.8) rwPFS 3.88 (2.8, 6.0) 3.22 (2.0, 5.7) TTD 3.06 (2.4, 3.5) 1.71 (1.7, 2.4) TTNT 3.45 (2.9, 4.5) 3.02 (1.9, 4.6)

Real-world (rw) treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic tx and avelumab 1L maintenance (1LM): Results from the IMPACT UC-III study.

390 Background: Avelumab 1LM is a standard of care for pts with mUC that has not progressed after 1L platinum-based chemotherapy (PBC). Immuno-oncology (IO) monotherapy is considered in pts with mUC who are ineligible to receive PBC. Recently approved 1L tx options include enfortumab vedotin + pembrolizumab and nivolumab + gemcitabine/cisplatin. This US retrospective study examined pt characteristics, tx patterns, and clinical outcomes among pts with mUC receiving 1L tx, including avelumab 1LM. Methods: Pts with mUC (bladder cancer; stage IIIB or IV, or ≥2 claims with ICD-10 diagnoses for metastatic cancer) aged ≥18 years, who initiated 1L tx (index date) from Jan 1, 2020 to Jul 31, 2023, were identified from the Healthcare Integrated Research Database (HIRD®; claims and clinical data from the health plan’s Cancer Care Quality Program). Clinical outcomes, including time to next tx (TTNT; time from 1L tx initiation to second-line tx) and overall survival (OS), were evaluated post index date. Pt characteristics and tx patterns were summarized using descriptive statistics. Avelumab 1LM use was identified on/after June 30, 2020 and ≤90 d after 1L PBC discontinuation. OS from the start of 1L tx or 1LM was analyzed using Kaplan-Meier methodology. Results: Of 2,820 pts with mUC, 1L tx was PBC in 37.0% (n=1,044), IO monotherapy in 39.0% (n=1,099), and other tx in 24.0% (n=677; antibody-drug conjugates and non-PBC). Among pts who received 1L PBC, 15.0% (n=157) initiated avelumab 1LM within 90 days of completing 1L PBC. Avelumab uptake in 2020-2023 by year was 10.8% (Jun-Dec 2020), 29.9%, 34.4%, and 24.8% (Jan-Aug 2023), respectively; 38.9% of pts were still receiving avelumab at the end of the study period. In the 1L PBC and IO cohorts, mean age (SD) was 65.5 (11.1) and 74.6 (10.7) years, respectively. 60% of pts were male. In the 1L PBC and 1L IO monotherapy cohorts, respectively, median follow-up (IQR) was 11.2 (5.6-20.3) and 8.6 (4.0-17.7) months (mo); median TTNT (IQR) was 4.8 (2.8-8.3) and 5.5 (2.8-11.0) mo; and median OS (95% CI) was 29.7 (25.1-37.2) and 20.0 (17.1-25.6) mo. In pts who received avelumab 1LM, median follow-up (IQR) from start of 1L PBC was 14.6 (9.2-21.3) mo; median TTNT (IQR) was 7.6 (6.2-12.3) mo; median time on avelumab tx was 5.0 (1.8-10.2) mo; and 1- and 2-year OS rates, respectively, from start of avelumab 1LM were 78% and 65%, and from start of 1L PBC were 84% and 68% (median OS was not estimable because &gt;50% of pts remained alive at the end of the study period). Conclusions: Despite advances in 1L tx for mUC, IO monotherapy remains a prevailing option for older, commercially insured patients in the US. In this descriptive rw study, pts treated with 1L PBC had longer OS than pts treated with 1L IO monotherapy. Future studies with longer follow-up are needed to further evaluate pt outcomes.