Interruption Rate Research Articles

Prescribing Pattern and Safety Profile of Biological Agents for Psoriasis in Real-World Practice: A Four-Year Calabrian Pharmacovigilance Analysis

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests.

What influences interruption of continuous renal replacement therapy in intensive care unit patients: A review with meta-analysis on outcome variables.

Evidence suggests that 8%-10% of ICU patients receive renal replacement therapy. However, there is a high rate of unplanned CRRT interruption, ranging between 17% and 74%. Studies on unplanned interruption of CRRT mainly focused on the retrospective investigation of related risk factors and conclusions have been diverse. This article aims to clarify the main influencing factors related to unplanned interruption of continuous renal replacement therapy (CRRT) in adult patients in intensive care units (ICUs). A literature review and meta-analysis were undertaken. Following the application of the Newcastle-Ottawa Scale (NOS), a total of 15 articles were included in a total of 2132 patients who underwent 3690 CRRT procedures and 2181 unplanned interruption times. The methodological guideline of a scoping review was applied for the evidence synthesis while applying the meta-analysis quantitative methodological guideline to identify and clarify main influencing factors related to unplanned interruption of CRRT. The reporting Prisma Protocol was followed. Longer filter life and prothrombin activation time, higher red blood cell count, greater transmembrane pressure, faster blood flow rate, intermittent saline irrigation, lower creatinine level, low prothrombin activity and pre-dilution are factors identified to potentially affect unplanned CRRT in ICU patients. Available evidence suggests four clinical challenges associated with unplanned CRRT interruption, namely: (a) effects of red blood cell count, filter life, cross-mode pressure, blood flow velocity, prothrombin activity and activated partial thrombin time on unplanned interruption; (b) influence of dilution mode on unplanned interruption; (c) influence of intermittent saline irrigation on unplanned interruption; (d) influence of Scr level on unplanned interruption. The potential to increase the ability to better manage unplanned CRRT in ICUs has been identified in this article and constitutes a relevant potential health care management contribution that can be implemented by nurses.

Contrast enhanced mammography (CEM) guided biopsy using a prone table: A retrospective analysis of the preliminary experience in a single CEM referral center

BackgroundThis study evaluates the procedural efficacy and patient experience of Contrast Enhanced Mammography (CEM)-guided biopsies performed in a prone position using the Giotto Class 30,000 system. The emphasis is on the procedural advantages and clinical outcomes for “enhancing-only lesions” (EOLs). MethodsA retrospective analysis of 524 CEM examinations conducted from December 2023 to June 2024 at a tertiary referral center was performed. Patients referred for pre-surgical staging or evaluation of inconclusive findings from conventional imaging were included. The study utilized dual-energy imaging and vacuum-assisted biopsy techniques, focusing on patients with at least one EOL identified in their initial CEM. Exclusions were based on the absence of a primary or follow-up CEM conducted at our facility Endpoints of this work included procedure efficiency which was evaluated in terms of technical success (biopsy completion with adequate sampling), dose distribution and timing and detection of additional lesions and patients’ comfort evaluation, based on the rate of complications (hematomas) and procedure interruption due to patients’ specific request or fainting events. ResultsAmong the evaluated cases, 37 EOLs were biopsied. The average procedure time was 15.8 min. Biopsies were successfully completed in 100% of cases. However, complications occurred in 27% of cases, primarily as hematomas and a significant histological finding rate of 97.3% was recorded. ConclusionsThe use of the Giotto Class 30,000 system for CEM-guided biopsies in a prone position demonstrated high procedural success and was well-tolerated by patients, highlighting its potential to enhance procedural comfort and efficiency. These preliminary results validate the innovative approach, though further studies are required to solidify these findings and explore long-term outcomes.

Barriers to the Completion of Radiation Therapy in Cervical Cancer Treatment in Nigeria: A Review of Socioeconomic, Geographical, and Psychosocial Factors.

Cervical cancer is a major health concern in Nigeria, where it is one of the primary causes of cancer-related deaths among women. Despite the crucial role of radiation therapy in treating cervical cancer, many patients in Nigeria do not complete their prescribed treatment courses. This review examines the barriers contributing to this issue. Factors such as low awareness and utilization of Pap smears, inadequate HPV vaccination, financial constraints, insufficient radiotherapy infrastructure, and the psychological burden of cancer treatment are explored. Limited screening and vaccination efforts exacerbate the high incidence of cervical cancer in Nigeria. Financial barriers are a primary obstacle, with many patients unable to afford the high cost of radiotherapy. Nigeria's radiotherapy infrastructure is severely lacking leading to significant treatment delays and cancellations. Geographical barriers further complicate access, as many patients must travel long distances to reach treatment centers. Psychosocial issues, including anxiety and depression, significantly impact treatment adherence and completion. These psychological factors, coupled with the physical side effects of radiotherapy, contribute to high rates of treatment interruption. To address these challenges, the review suggests enhancing cervical cancer prevention through increased human papillomavirus (HPV) vaccination and screening, expanding radiotherapy capacity by increasing the number of treatment centers, and providing comprehensive support systems to address financial and psychosocial barriers. By implementing these strategies, it is possible to improve treatment adherence and outcomes for cervical cancer patients in Nigeria.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Introduction and ObjectivesAutoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. Materials and Methods107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. ResultsHCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). ConclusionsIn summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.

Adherence to Short-Duration Treatment (3HP) for Latent Tuberculosis among International Migrants in Manaus, Amazonas: Evaluation of the Efficacy of Different Treatment Modalities.

Migration, a multifaceted phenomenon, has a significant impact on health. Migrants perform similar movement patterns within their country of origin, in transit, and in the country of destination, thus making it difficult to monitor TB treatment throughout the journey. The objective was to compare the effectiveness of different treatment modalities in adherence to the short-term regimen for LTBI (3HP) among international migrants and refugees. This is a quasi-experimental study conducted in Manaus-AM. The study population was made up of international migrants. The certification and monitoring of medication intake employed three strategies: self-administration (SA), directly observed conventional therapy (DOT), and Video Telemonitoring System for Tuberculosis Treatment (VDOT). The VDOT group and SA group exhibited the lowest rate of treatment dropout or interruption at 16.1%, followed by the DOT group at 23.1%. The results suggest that the most effective strategy for ensuring adherence among migrants and refugees was VDOT (OR_adj 0.26; CI 0.7-0.94), suggesting that migrants may be more likely to adhere to and complete their treatment. The results show that relying on different treatment strategies, adapted to the individuals' needs and risk factors, is a viable and effective way of providing person-centered TB care.

Development and validation of a predictive scoring model for risk stratification of tuberculosis treatment interruption

BackgroundTuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission. ObjectivesThis study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption. MethodsA multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance. ResultsOf 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0–2), medium (3–5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001). ConclusionThe predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase.

Mean-square exponential stabilization of memristive neural networks: Dealing with replay attacks and communication interruptions

This paper investigates the mean-square exponential stabilization (MSES) of memristive neural networks (MNNs) under replay attacks and communication interruptions. The research will revolve around the following two questions: Firstly, facing replay attacks and communication interruptions, how to design an appropriate controller? Secondly, how to ensure the MSES of MNNs under higher replay attack rate and communication interruption rate? To address these challenges, a novel intermittent sampled-data control scheme is established by considering the mathematical characteristics of replay attacks and communication interruptions. Furthermore, interval-dependent Lyapunov functions are constructed based on the Lyapunov stability theory and inequalities techniques, and two sufficient criteria for MSES of MNNs under the mentioned risks are derived. Thus, the control gain is obtained by solving a series of linear matrix inequalities. In addition, two algorithms are designed to investigate the maximum allowable replay attack rate and communication interruption rate for the system, respectively. Finally, two numerical examples are given to verify the effectiveness of the proposed scheme.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants

PurposeFacilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically.MethodsThis phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint.ResultsOf 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms.ConclusionThe favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.

Effectiveness of Outreach Clinical Mentoring on Retention in Care and Viral Suppression among HIV Positive Young Persons on Art in North Central Nigeria

Introduction Sexual and reproductive health challenges vis-à-vis Human immunodeficiency virus/Acquired immune deficiency syndrome, constitute a complex phenomenon in young persons. These health complexes have been shown to adversely affect the disclosure of their positive status, their adherence to medications or retention in care and overall quality of life. This study was meant to determine the effectiveness of deliberate clinical mentoring on retention in care, measured by the rate of interruption in treatment and viral suppression among young persons on anti-retroviral therapy.  Methods This study employed a facility-based quasi- experimental design. A multi-stage sampling technique was used to select study participants. The three senatorial zones of Nasarawa state were selected through a purposive sampling method at stage one. One Local Government Area was selected from each of the three senatorial zones through simple random sampling technique at stage two. Five health care facilities were randomly selected from each of the three selected Local Government Areas through balloting at stage three. Baseline data was collected at the beginning of the study; mid-term data mid- way into the study and post-intervention data was collected at the end of the study. The respondents/mentees were mentored for a period of eight months.  Results Difference in means of interruption in treatment rates at baseline and at midterm, which is an estimate of the amount by which intervention changed the outcome was – 0.69605 with a p-value of 0.359. Mean differences in interruption in treatment rates pre- and post-intervention was 0.7333 with a p-value of 0.033, which was statistically significant. In a similar vein, mean differences in viral suppression rates at start of study and mid-term on the one hand, and then pre- and post-intervention on the other hand, were respectively 4.80000 and 3.40000. The corresponding p-values were 0.235 and 0.174, which were not statistically significant.  Conclusion This study showed 100% retention among young persons on anti-retroviral therapy following 8 months of meticulous outreach clinical mentoring. The study also showed improvements in viral suppression rates, but the extent statistically, was not significant. Clinical mentoring should therefore, be prioritized and strengthened for better clinical care outcomes in positive young persons on anti retroviral therapy.

Virtual reality simulation to enhance advanced trauma life support trainings – a randomized controlled trial

BackgroundAdvanced Trauma Life Support (ATLS) is the gold standard of initial assessment of trauma patients and therefore a widely used training program for medical professionals. Practical application of the knowledge taught can be challenging for medical students and inexperienced clinicians. Simulation-based training, including virtual reality (VR), has proven to be a valuable adjunct to real-world experiences in trauma education. Previous studies have demonstrated the effectiveness of VR simulations for surgical and technical skills training. However, there is limited evidence on VR simulation training specifically for trauma education, particularly within the ATLS curriculum. The purpose of this pilot study is to evaluate the feasibility, effectiveness, and acceptance of using a fully immersive VR trauma simulation to prepare medical students for the ATLS course.MethodsThis was a prospective randomised controlled pilot study on a convenience sample of advanced medical students (n = 56; intervention group with adjunct training using a commercially available semi-automated trauma VR simulation, n = 28, vs control group, n = 28) taking part in the ATLS course of the Military Physician Officer School.Feasibility was assessed by evaluating factors related to technical factors of the VR training (e.g. rate of interruptions and premature termination). Objective and subjective effectiveness was assessed using confidence ratings at four pre-specified points in the curriculum, validated surveys, clinical scenario scores, multiple choice knowledge tests, and ATLS final clinical scenario and course pass rates. Acceptance was measured using validated instruments to assess variables of media use (Technology acceptance, usability, presence and immersion, workload, and user satisfaction).ResultsThe feasibility assessment demonstrated that only one premature termination occurred and that all remaining participants in the intervention group correctly stabilised the patient. No significant differences between the two groups in terms of objective effectiveness were observed (p = 0.832 and p = 0.237 for the pretest and final knowledge test, respectively; p = 0.485 for the pass rates for the final clinical scenario on the first attempt; all participants passed the ATLS course). In terms of subjective effectiveness, the authors found significantly improved confidence post-VR intervention (p < .001) in providing emergency care using the ATLS principles. Perceived usefulness in the TEI was stated with a mean of 4 (SD 0.8; range 0–5). Overall acceptance and usability of the VR simulation was rated as positive (System Usability Scale total score mean 79.4 (SD 11.3, range 0–100).ConclusionsThe findings of this prospective pilot study indicate the potential of using VR trauma simulations as a feasible and acceptable supplementary tool for the ATLS training course. Where objective effectiveness regarding test and scenario scores remained unchanged, subjective effectiveness demonstrated improvement.Future research should focus on identifying specific scenarios and domains where VR can outperform or enhance traditional learning methods in trauma simulation.

Symptom management through electronic patient-reported outcome (ePRO)-based intervention in patients with breast cancer treated with abemaciclib: Primary results from the LIBRA study, a phase II randomized controlled trial.

11110 Background: We have developed a system using LINE, a widely-used social network service in Japan, for rapid collection of ePROs based on the PRO-CTCAE criteria. To evaluate the effectiveness of intervention through this system in reducing diarrhea frequency and enhancing quality of life (QOL) in patients treated with abemaciclib, we conducted a randomized controlled trial. Methods: Patients with hormone receptor-positive advanced breast cancer scheduled to begin abemaciclib treatment were randomized to the intervention and control arms with 1:1 ratio. The LINE-ePRO system was used to monitor symptoms daily in both arms. In the intervention arm, expert medical staffs contacted patients via phone when symptoms met certain criteria, whereas patients in the control arm received standard care. The primary endpoint was the increase in the number of defecations from baseline during 28 days. The secondary endpoints included the increase in the number of defecations from baseline during 56 days, other symptoms monitored via the LINE-ePRO system, QOL evaluated by EORTC QLQ C-30 and EQ-5D-5L, relative dose intensity (RDI), treatment interruption rate, progression-free survival (PFS), and overall survival (OS). This study (LIBRA, UMIN000045432) is funded by Eli Lilly. Results: Between Jan 2022 and Apr 2023, 60 women were enrolled and 58 (29 in each arm) were analyzed in this study. Median age was 57.5 years (range 43-80), 93% of patients were post-menopausal, 71% received abemaciclib as first-line treatment, and 74% were treated in combination with aromatase inhibitors. The increase in the number of defecations from baseline was significantly lower in the intervention arm compared to the control arm both during 28 days (0.64 vs. 1.21 per day, p=0.003) and during 56 days (0.55 vs. 1.18 per day, p=0.0004). No significant difference was observed in other symptoms between the arms. In the EORTC QLQ C-30 scales, global health status/QOL (mean score change from baseline to after one cycle of abemaciclib treatment: 0 vs. -13.5, p=0.038) and diarrhea (20.7 vs. 32.2, p=0.049) were better in the intervention arm. The treatment interruption and dose reduction rates were 41.4 and 31.0% in the intervention arm, and 31.0 and 27.6% in the control arm, respectively. The mean RDI of abemaciclib was numerically lower in the intervention arm (73.5% vs. 84.8%). Conclusions: This study is the first randomized trial to demonstrate that the intervention based on daily ePROs reduces the frequency of diarrhea in patients with advanced breast cancer treated with abemaciclib. Clinical trial information: UMIN000045432.

Real world experience of trastuzumab deruxtecan for the treatment of metastatic breast cancer in the UK.

1024 Background: Trastuzumab deruxtecan (TDXd), an antibody drug conjugate, was first approved in the UK for the treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in 2021. We aimed to review the efficacy and tolerability of TDXd in a real-world UK setting. Methods: We collected clinical and demographic data from medical records on HER2+ mBC patients treated with TDXd in the UK from Jan 2021 to Dec 2023 inclusive. This included: radiological response, the frequency of dose reductions and treatment delays, and reasons for discontinuation. Clinical trial patients were excluded. Descriptive statistical techniques were applied. Results: Data was collected from 26 UK cancer centres on 280 patients. The median age at TDXd initiation was 56 years (range 29-85). Median treatment duration was 9 cycles (range 1-40). 239 patients (85%) had visceral disease. 257 and 196 patients (92% and 70%, respectively) had received prior Trastuzumab and Pertuzumab, respectively. 233 patients (83%) had received prior TDM1. The median number of lines of treatment prior to TDXd was 3 (range 1 to 9). 20 patients (7%) were initiated on a reduced dose and 115 further patients (41%) required at least one dose reduction. 151 patients (54%) had at least one dose interruption due to: infection or neutropenia (n=61), other toxicity (n=85), interstitial lung disease (ILD) investigation (n=39), patient request (n=81), other concurrent illness (n=10), and cardiac investigation (n=6). Of these, 55 patients had more than one treatment break. 157 patients (56%) had discontinued TDXd treatment due to: disease progression or death (n=100), drug toxicity (n=39) of which 22 were due to ILD, and patient choice (n=8). 123 patients remained treatment at the time of analysis. The overall response rate of TDXd was 63% overall: stable disease 23%, partial response 56%, complete response 7%. Conclusions: The real-world data set is not directly comparable to either the DB02 or DB03 trials, as it included patients who had received TDXd in both the second line and later line settings. However, the majority (80%) of these patients were treated in the third line and beyond. The rates of drug interruption and reduction were higher in the real-world data set than in DB02, which may impact on efficacy in the real-world setting. Overall response rate is similar between trial data and our real-world data, although the latter was not measured by RECIST. Data collection is ongoing, including an analysis of real-world progression free survival. [Table: see text]

Pooled analysis on characteristics of nausea and vomiting in patients receiving trastuzumab deruxtecan (T-DXd) in clinical studies.

12118 Background: The efficacy and safety profile of T-DXd has been established in patients (pts) with various tumor types, and nausea and vomiting are the most common treatment-emergent adverse events (TEAEs). T-DXd study protocols were refined over time to recommend prophylaxis (eg, neurokinin or serotonin receptor antagonists and/or steroids) before T-DXd treatment, in line with antiemetic and institutional guidelines. We conducted a pooled, post hoc analysis capturing safety information across tumor types; we report results on nausea and vomiting. While this analysis was not designed to assess antiemetic effectiveness, it reveals the incidence of nausea and vomiting in clinical trials of T-DXd 5.4 mg/kg in more detail across a large dataset. Methods: 1449 pts treated with ≥1 dose of 5.4 mg/kg T-DXd (every 3 wks) were included from 7 phase 1-3 clinical trials in metastatic HER2+ and HER2-low breast cancer, HER2+ gastric cancer, and HER2-mutant non–small cell lung cancer (DESTINY-Breast01, -Breast02, -Breast03, -Breast04, -Lung01, -Lung02, and the first-in-human phase 1 study J101 in multiple tumor types; study enrollment starting 2015-2021). Regardless of antiemetic use (including prophylaxis), the incidence, severity, time to onset, and duration of nausea and vomiting TEAEs were assessed along with event outcomes. Results: Of 1449 pts receiving T-DXd 5.4 mg/kg (median [range] number of 3-wk treatment cycles: 13 [1-60]), 74.6% (n=1081) experienced nausea, and 41.6% (n=603) reported vomiting. Most pts had grade 1/2 nausea (41.2%/27.6%) and/or vomiting (26.2%/12.8%). Grade 3 TEAEs of nausea were reported in 5.8% of pts, with grade ≥3 TEAEs of vomiting observed in 2.6% of pts. By the data cutoff for each trial, 66.9% of pts with nausea and 87.6% with vomiting had their symptoms resolve. Most pts who experienced nausea and vomiting did so during the initial 21 days (cycle 1; n=879 [81.3%] and 336 [55.7%], respectively; 35.8% of all pts received antiemetic prophylaxis at cycle 1); both TEAEs declined notably in subsequent cycles. Rates of drug discontinuation, dose reduction, and drug interruption due to nausea and vomiting were generally low (Table). Conclusions: Most nausea and vomiting events were reported during the first 3 wks of treatment and resolved. Appropriate prophylaxis of nausea and vomiting is a key management strategy and allows pts to benefit from longer treatment durations with T-DXd. Ongoing studies are exploring the implementation and impact of prophylaxis for T-DXd–related emesis. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 , NCT03734029 , NCT03505710 , NCT04644237 , NCT02564900 . [Table: see text]

Real-world safety and discontinuation rates of fam-trastuzumab deruxtecan in advanced HER2-positive and HER2-low cancer.

e12518 Background: Fam-trastuzumab deruxtecan’s (Enhertu) 2022 approval for HER2-low breast cancer spurred widespread adoption of its utilization. DESTINY-Breast04 trial reported 9.9 months median progression-free survival (PFS); however, 16.2% experienced adverse events leading to treatment discontinuation. Our study evaluates real-world adverse event rates causing treatment discontinuation, to assess Enhertu's safety in patients with advanced metastatic cancer. Methods: A retrospective analysis was conducted at a community-based practice in Kansas, USA from 2020 to 2024. 99 patients with HER2-positive and HER2-low cancer, treated with Enhertu, with ECOG performance status of 0 and 1 were identified. Absolute values and proportions were used to represent categorical and nominal variables. Proportions between groups were analyzed using the likelihood ratio chi-square, Fisher's test, and the z-test. Statistical analyses were performed using SAS 9.4. The primary objective was to determine treatment discontinuation rates due to adverse events, while secondary objectives included assessing discontinuation rates due to disease progression, mortality rates, as well as progression-free survival, and dose interruption rates. Results: The average age of patients was 62 years, with 92% being females. The most common cancer types treated were Stage IV metastatic Breast Cancer (87%) and Gastric/Gastroesophageal Junction Cancer (9.1%). Of these cases, 44% were HER2-positive, while the rest were HER2-low. A total of 74% of patients discontinued treatment, with a mean duration of 5.4 months (95% Confidence Interval [CI] 4.2-6.7). Adverse events accounted for 9% of discontinuations, including interstitial lung disease/pneumonitis (33%), thrombocytopenia (11%), diarrhea (11%), nausea (22%), and dysgeusia (11%). 77% experienced grade 2 and 3 adverse events. Disease progression and death resulted in 49.4% and 11% of Enhertu discontinuation respectively. Among patients still on Enhertu (26%), the mean treatment duration was 13.5 months (95% CI 9.5-17.5). The mean PFS was 9.3 months (95% CI 6.2-9.4). Dose interruptions due to adverse events with subsequent resumption occurred in 18% of patients. Conclusions: In our community-based observational study on Enhertu discontinuation rates due to treatment-emergent adverse events (TEAEs), we found a 9% discontinuation rate—significantly lower than the 16.2% reported in the Breast04 trial, (P=0.045). The incidence of interstitial lung disease was 3%, considerably less than the 12% reported in Breast04. Importantly, no deaths related to TEAEs were observed, suggesting a lower occurrence of serious adverse events in clinical practice compared to clinical trials. These results underscore Enhertu's safety profile in advanced metastatic HER2-positive and low cancer.

FAPR: An Adaptive Approach to Link Failure Recovery in SDN with High Speed and Low Interruption Rate

FAPR: An Adaptive Approach to Link Failure Recovery in SDN with High Speed and Low Interruption Rate

Management of edoxaban therapy in patients undergoing emergency/urgent procedures: a subanalysis of the global, prospective, observational, multinational EMIT-AF/VTE programme

Abstract Background Physicians are often unable to follow recommendations for preprocedural oral anticoagulant interruption before emergency/urgent (unplanned) procedures, which may lead to a higher incidence of adverse outcomes in these patients compared with those who undergo planned procedures. The Global EMIT-AF/VTE programme found low bleeding and thromboembolic event rates for patients receiving edoxaban who underwent diagnostic or therapeutic procedures. However, edoxaban management and clinical outcomes may differ among the subgroup of patients with emergency/urgent procedures. Purpose To describe periprocedural edoxaban management and clinical outcomes for patients in the EMIT-AF/VTE programme who underwent emergency/urgent procedures. Methods In this subanalysis, only physician-reported unplanned (emergency/urgent) procedures were included, of which dental and dermatological procedures were excluded. Only a patient’s first emergency procedure was included, with the exception of 3 patients having 2 procedures on the same day (in these cases the 2 procedures were combined). Procedure bleeding risk was classified according to EHRA criteria, and baseline characteristics and edoxaban interruption data were collected. Clinical event and procedure dates were compared to determine whether they were related. Results Among 156 patients undergoing emergency/urgent procedures, the mean ± standard deviation age at baseline was 74.5 ± 8.7 years, and the CHA2DS2-VASc score was 3.8 ± 1.6. Medical histories of hypertension and dyslipidaemia were reported in 84.0% and 40.4% of patients, respectively; approximately one-quarter of patients had diabetes mellitus (26.9%) or creatinine clearance ≤50 mL/min (24.4%). The most common procedure types were vascular access and transcatheter diagnostics/interventions (34.6%) and gastroenterological procedures (27.6%). Procedures were more often EHRA-classified as minor (35.9%) or low (35.3%) vs high risk (20.5%). Preprocedure edoxaban interruption rates ranged from 39.3%–50.9% across risk groups, with more than half of the procedures being performed with edoxaban interruption (53%–66%; Figure). By 20 days postprocedure, edoxaban therapy was resumed in approximately 86% and 88% of patients with minor- or low-risk procedures vs 70% with high-risk procedures. Overall, 33 clinical events were recorded, of which 18 (54.5%) preceded a procedure (Table). Five bleeding events and one thrombotic event occurred after and were caused by the procedure. Conclusions Edoxaban resumption was protracted after high- vs minor- or low-risk procedures. Bleeding and thrombotic events resulting from a procedure occurred in &amp;lt;4% of patients, indicating that postprocedure edoxaban therapy can be effectively tailored to optimise clinical outcomes.FigureTable

Impact of childhood traumatic brain injury on fitness for service class, length of service period, and cognitive performance during military service in Finland from 1998 to 2018: A retrospective register-based nationwide cohort study.

Traumatic brain injury (TBI) can cause neuronal damage and cerebrovascular dysfunction, leading to acute brain dysfunction and considerable physical and mental impairment long after initial injury. Our goal was to assess the impact of pediatric TBI (pTBI) on military service, completed by 65-70% of men in Finland. We conducted a retrospective register-based nationwide cohort study. All patients aged 0 to 17 years at the time of TBI, between 1998 and 2018, were included. Operatively and conservatively treated patients with pTBI were analyzed separately. The reference group was comprised of individuals with upper and lower extremity fractures. Information on length of service time, service completion, fitness for service class, and cognitive performance in a basic cognitive test (b-test) was gathered from the Finnish Military Records for both groups. Linear and logistic regression with 95% CI were used in comparisons. Our study group comprised 12 281 patients with pTBI and 20 338 reference group patients who participated in conscription. A total of 8 507 (66.5%) men in the pTBI group and 14 953 (71.2%) men in the reference group completed military service during the follow-up period. Men in the reference group were more likely to complete military service (OR 1.26, CI 1.18-1.34). A total of 31 (23.3%) men with operatively treated pTBI completed the military service. Men with conservatively treated pTBI had a much higher service rate (OR 7.20, CI 4.73-11.1). In the pTBI group, men (OR 1.26, CI 1.18-1.34) and women (OR 2.05, CI 1.27-3.36) were more likely to interrupt military service than the reference group. The PTBI group scored 0.15 points (CI 0.10-0.20) less than the reference group in cognitive b-test. PTBI groups had slightly shorter military service periods and higher interruption rate than our reference-group. There were only minor differences between groups in cognitive b-test.

Diagnosis, management, and outcomes of immune checkpoint inhibitor induced acute interstitial nephritis: A single-center experience.

Immune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (AIN) is a recognized complication of immunotherapy (IO), but literature on its management and outcomes is limited. We retrospectively reviewed patients who received ICIs and developed biopsy-proven or clinically-suspected ICI-associated AIN at the University of Virginia Comprehensive Cancer Center from 2012-2023. We analyzed baseline characteristics and clinical outcomes, including treatment interruption and rechallenge rates. Acute kidney injury (AKI) was defined as a ≥ 1.5-fold increase in baseline creatinine under seven days, a two-fold increase above the upper limit of normal, or an increase by ≥0.3 mg/dL. Kidney function returning to within 0.3 mg/dL or less than twice baseline was considered complete (CRc) and partial (PRc) recovery, respectively. We identified 12 cases of ICI-AIN: four by biopsy (33%) and eight (67%) by clinical suspicion. Two patients received anti-CTLA-4 and anti-PD1, six received anti-PD1 alone, and four received chemo-immunotherapy. The majority (58%) of patients developed AIN within the first 5 cycles. Eight patients developed ≥ Grade 3 AKI, and six developed multiple irAEs. ICI was permanently discontinued in seven patients (58%) and temporarily interrupted in four (30%). The CRc and PRc rates were 67% and 8%, respectively. Upon AIN onset, the best disease response was stable disease in five patients, partial response in three, and progressive disease in three. Median overall survival was 4.87 years, and progression-free survival was 1.5 years. Rechallenge with IO after kidney irAE may be possible in some patients but requires careful evaluation on an individual basis.

Abstract PO4-27-04: GRACE-trial: A randomized active-controlled trial for vulvovaginal atrophy in breast cancer patients on endocrine therapy

Abstract Background: Breast cancer is the most common cancer type in women worldwide. Due to hormone receptor positivity in the majority of the breast cancer tumors is endocrine therapy a crucial part in the treatment landscape of breast cancer. Selective estrogen-receptor modulators or aromatase inhibitors are the used treatment options for endocrine therapy. These medicines generate a hypoestrogenic environment by reducing circulating estrogen or by altering the effect of estrogen on tissue cells by receptor blockade. As a common side effect, vulvovaginal atrophy occurs in a majority of breast cancer patients using endocrine therapy. Vulvovaginal atrophy has a significant impact on physical and psychological wellbeing due to negative influence on quality-of-life, self-esteem and sexuality. As a consequence, adherence of endocrine therapy for the standard duration of 5 to 10 years is challenging, resulting in higher rates of therapy interruption, leading to poorer prognosis with shorter distant disease free survival. The standard treatment for vulvovaginal atrophy in postmenopausal women is based on the use of local hormonal treatment. However, when a patient has a history of breast cancer, delay of treatment and undertreatment are ubiquitous. Methods &amp; design: In this first ever prospective randomized trial breast cancer patients on endocrine therapy with vulvovaginal atrophy will be treated with the available local treatment modalities with a 1:1:1:1 randomization: estrogen, dehydroepiandrosterone, moisturizers and a co-treatment of estrogen and probiotics. Patient-reported outcomes measurements will be implemented to investigate the efficacy of the implemented treatments. These outcome measures include symptom evaluation, impact on quality-of-life and sexuality. Safety of the treatments will be evaluated by assessing systemic sex hormones concentrations. Previous research indicated no increased recurrence risk, yet no randomized trials comparing the different modalities have been published. Primary objectives: Two primary objectives have been determined. Firstly, the efficacy of the different treatment modalities will be assessed. The assessment will be based on patient-reported outcome measurements (PROMs) and clinical evaluations such as vaginal pH and the vaginal maturation index, the latter a direct microscopic evaluation of the vaginal epithelium. Secondly, safety of the different groups will be assessed. Evaluation will be done be measuring sex hormone concentrations systemically, which will be a surrogate for safety evaluation. Secondary objectives: The secondary objective in this study is the identification of microbial alterations after treatment initiation. Identification of these alterations can help in further understanding of the pathophysiology of vulvovaginal atrophy and potentially create opportunities for new treatment strategies towards vulvovaginal atrophy in breast cancer patients on endocrine therapy. Registration: The current study is registered at the European Union Clinical Trials Register (EudraCT number 2021-001921-31). Trial status: Recruitment for the study was commenced in May 2022. At time of manuscript submission, patient recruitment was ongoing. Citation Format: Glenn Vergauwen, Piet Cools, Hannelore Denys, Tom Fiers, Koen van de Vijver, Liv Veldeman, Hans Verstraelen. GRACE-trial: A randomized active-controlled trial for vulvovaginal atrophy in breast cancer patients on endocrine therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-04.