Safety Of Treatment In Patients Research Articles

Brain metastases and anticoagulant therapy: Safety and outcome in a real-world study.

e14016 Background: The increasing overall survival in cancer patients, due to advances in diagnostics and treatments, lead to an expected increase in diagnoses of brain metastasis (BM). A relevant feature in care-management of this special population is the safety in anticoagulant therapies administration, since cancer-associated thrombosis (CAT) is a concrete complication in patients with BM. In BM patients the risk of developing AEs increase with local treatments (i.e. radiation), and bleeding is a critical issue. Hence, understanding the risk/benefit ratio of anticoagulants in BM is mandatory. We conduct an observational, retrospective study collecting data from patients with BM diagnosis who underwent anti-cancer treatment and had at least a 3 months follow-up. We collect clinical characteristics, treatment, outcome, AEs concomitant medication with a focus on anticoagulants. Finally we assess the correlations between cardiovascular risk factors and increasing bleeding risk with anticoagulants. Methods: The study is observational, retrospective and single center. We included 148 patients with radiological evidence of BM who have at least 3 months follow-up after BM diagnosis. Patients were in charge of Medical Oncology Unit in Careggi University Hospital between 2015 and 2022. Data were collected from medical records. Results: We collected data from 148 patients with BM. Primary cancers were NSCLC (66%; n=98), breast (11%) and melanoma (6%) among the most common. Of the patients described, 87% (n=129) had an ECOG PS 0-1 and clinical condition was complicated by comorbidities as per hypertension (45%), COPD (15%) and diabetes (13%). Radiation was the most locoregional treatments performed (78%; n=115). Patients undergoing systemic treatments, had chemotherapy (51%), immunotherapy (24%) and TKIs (12%) after diagnosis of BM, and a DCR of 75% was achieved. 34% of patients with BM in NSCLC received anticoagulants therapy (n=33). Patients underwent LMWH (n=18) and fondaparinux (n=12), while NAOs were less common (n=5). The treatment goal was VTE prophylaxis, treatment of VTE or PTE respectively in 24% of patients; in 21% of patients anticoagulants were administered as prevention of AF complications. Regarding AEs, there were only one episode of minor hemorrhage (associated with NAO). Although statistical significance was not reached, we highlight a trend between VTE and hypertension in NSCLC population ( p=0.069) and between VTE and smoking history ( p=0.056) in the total population with BM. Conclusions: The use and safety of anticoagulant treatments in patients with BM have recently gained considerable importance. Our data do not allow us to draw conclusions about the safety of using NAOs or LMWHs in a population with BM. The retrospective nature and smallness of our sample suggest the need for further population studies with larger samples.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Central nervous system (CNS) involvement in patients with refractory or relapsed large B-cell lymphoma (LBCL) is associated with an extremely poor prognosis. Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an approved treatment for patients with refractory or relapsed (R/R) LBCL that has changed the prognosis of patients with chemoresistant LBCL. However, data regarding efficacy and safety of CART cell treatment in patients with active CNS involvement are limited since they are excluded from most of clinical trials. Methods: We retrospectively collected data from 75 patients with LBCL, treated with CART cells from January 2020 to January 2023 in Henri Mondor Hospital. We identified 13 patients with active CNS involvement at the time of CAR-T cell treatment decision: 12/13 had abnormal neurological examination, 8/11 had head and/or medullar MRI abnormalities consistent with lymphoma and 9/10 had detectable lymphoma cells in the cerebrospinal fluid. We compared the characteristics of the 13 patients with CNS involvement (CNS+) with 62 patients without evidence of active CNS disease (CNS-). Median age was 69 and 59 years, respectively (p = 0.05). CNS+ patients received a median of 2 previous lines of treatment versus 3 for CNS- patients (p = 0.34). Performance status prior to CART-cell injection was 2 or more in 9/13 (69%) and 11/62 (18%) p < 0.001, respectively. 5/13 (38%) CNS+ patients had high grade B-cell lymphomas versus 11/62 (18%) CNS- (p = 0.13). CAR-T-cell was axi-cel in 10/13 (77%) CNS+ patients versus 42/62 (68%) CNS– (p = 0.74). It is noteworthy that 7/13 (54%) CNS+ patients had pre-existing low-grade B-cell lymphomas versus 15/62 (24%) CNS- (p = 0.046). Results: The best overall response rate was identical in both groups: 12/13 (92%) in CNS+ patients versus 51/61 (92%) in CNS-, including 11/13 (85%) and 44/61(72%) complete metabolic response. As shown in the figure, median progression free survival and overall survival was 5.5 and 8.4 months, respectively in CNS+ patients versus 11.5 and 21 months in CNS- patients (not significant). Regarding safety, 13/13 (100%) CNS+ patients had a cytokine release syndrome (10 grade 1–2 and 3 grade 3) versus 54/62 (87%) CNS- (49 grade 1–2 and 5 grade 3–4) and 10/13 (77%) experienced ICANS (6 grade 1–2 and 4 grade 3–4) versus 28/62 (45%) CNS- (27 grade 1–2 and 1 grade 3–4) (p = 0.06 and 0.02 for grade 3–4). Transfer into an intensive care unit occurred in 4/13 (31%) CNS+ patients versus 9/62 (15%) CNS- (p = 022). Median time of hospitalization was 37 days for CNS+ patients versus 20 days for CNS- patients (p = 0.007). Six CNS+ patients died from which 5 died of progression and 1 of infection. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Immunotherapy Conflicts of interests pertinent to the abstract. F. Lemonnier Consultant or advisory role: BMS, Kiowa, Miltenyi Educational grants: Gilead, Janssen, Roche L. Roulin Educational grants: Kite gilead, Novartis, Bristol myers squibb

Efficacy and safety of first-line treatments for patients with advanced hepatocellular carcinoma: A systematic review and network meta-analysis.

4094 Background: In recent years, the first-line treatment options for advanced HCC has been increasingly abundant, including transarterial therapies, combination of the immune checkpoint inhibitors (ICIs) and the anti-vascular endothelial growth factor (VEGF) inhibitor, ICIs combined with ICIs, and tyrosine kinase inhibitors. However, it remains to be confusing which treatment pattern would benefit people most, especially for different subgroups. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings for III phase randomized clinical trials (RCTs) investigating first-line treatments for HCC compared with sorafenib. The survival outcomes and toxic effects of RCTs should be reported, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of grade 3 or higher. This systematic review was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. The random-effects model was used to calculate the summary hazard ratios (HRs) of OS and PFS. The likelihood of ORR, and AEs of grade 3 or higher was performed by odds ratios (ORs) using a random-effects model. Results: A total of 13 phase III RCTs involving 8505 patients were included in this study. Hepatic arterial infusion of oxaliplatin combined with fluorouracil (FOHAIC-1) showed OS, PFS, and ORR benefit over all other first-line therapies, except for the regimen of sorafenib plus HAIC of FOLFOX (OS: HR, 0.88; 95% CI, 0.37-2.09; ORR: OR, 1.53; 95% CI, 0.29-8.13). More importantly, we found that sorafenib combined with FOLFOX was superior to other regimens in patients with HBV infection regarding OS except FOHAIC-1 (HR, 0.57; 95%CI, 0.21-1.52) and tremelimumab-durvalumab (HR, 0.42; 95%CI, 0.16-1.11). While in HCV-infected subgroup, ICIs combined with anti-VEGF inhibitor improved OS benefit compared with tremelimumab-durvalumab (HR, 0.31; 95% CI, 0.11-0.84) and sorafenib (HR, 0.38; 95% CI, 0.16-0.88). HAIC-FO also showed significant OS benefits to other therapies in patients with portal invasion or extrahepatic metastasis. The probability of adverse events of grade 3 or higher was significantly lower with HAIC-FO than with others except for nivolumab (RR, 0.96; 95%CI, 0.51-1.82) and tislelizumab (RR, 0.57; 95%CI, 0.30-1.08). Conclusions: This network meta-analysis supports arterial infusion as the first-line treatment for patients with HCC. In portal invasion and extrahepatic metastasis subgroups, HAIC-FO may be a preferred option, with sorafenib combined with FOLFOX as an additional option in those with HBV infection. Besides, novel combination therapy should be focused on in patients with certain subgroups.

Efficacy and safety of early ferric carboxymaltose treatment in patients with acute decompensated heart failure

BACKGROUND: The efficacy of intravenous ferric carboxymaltose (FCM) therapy in heart failure (HF) with low ejection fraction with iron deficiency (ID) or ID anemia is known. The aim of this study was to determine the efficacy and safety of intravenous FCM therapy in the early decompensated period in acute decompensated HF with low ejection fraction with ID or ID anemia.METHODS: Patients with acute decompensated HF with low ejection fraction (EF<40%) with ID or ID anemia were included in the study. ID was diagnosed according to serum ferritin and transferrin saturation (TSAT) measurement at admission in 26 patients and before discharge in 26 patients, and intravenous FCM treatment was given at the same time. ID was defined as serum ferritin <100 μg/L (absolute ID) or ferritin 100-299 μg/L with a TSAT<20% (functional ID). Cox regression analysis was used to determine the relationship between the time of intravenous iron therapy and the risk of 30-day hospitalization and 6-month rehospitalization and mortality and Linear regression analysis was used for N-terminal pro-brain natriuretic peptide (NT-proBNP) change at 30 days.RESULTS: All patients have either ID or ID anemia. The mean age was 67.0±13.0 years, 58% female. Anemia was more prevalent at admission blood samples than before discharge (P<0.001), and absolute and functional iron deficiency rates were similar (P=0.38 and P=0.19, respectively). 30-day rehospitalization (Hazar ratio [HR]= 0.80, confidence interval [CI] 0.22-2.98, P=0.74) Sixth-month rehospitalization (HR=0.89, CI 0.36-2.20, P=0.80) and Sixth-month mortality (HR=0.51, CI 0.05-5.56, P=0.58) were similar between treatment groups. There was no significant relationship between the time of administration of FCM treatment and the change in pro-BNP levels measured at baseline and 30-day (P=0.90).CONCLUSIONS: In patients with acute decompensated HF with low ejection fraction and ID or ID anemia, the efficacy and safety of intravenous iron therapy applied at admission are similar to before discharge.

Long-term Efficacy and Safety of Symptom-driven Cyclic Rozanolixizumab Treatment in Patients with Generalized Myasthenia Gravis: A Pooled Analysis of a Phase 3 Study and Two Open-label Extension Studies (P1-5.012)

Long-term Efficacy and Safety of Symptom-driven Cyclic Rozanolixizumab Treatment in Patients with Generalized Myasthenia Gravis: A Pooled Analysis of a Phase 3 Study and Two Open-label Extension Studies (P1-5.012)

Abstract CT170: Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors

Abstract A novel approach for cancer therapy was developed, comprising of magnetic multicore iron oxide nanoparticles (SaNPs) and alternating magnetic field (AMF) application. SaNPs are administered IV to the patient and accumulate in tumors through the enhanced permeability and retention (EPR) effect. The patient then undergoes regional AMF application (300kHz) that is converted to thermal energy, inducing sub-ablative hyperthermic cancer cell death. Based on extensive pre-clinical testing, treatment was proven safe and biocompatible in animal models without any associated toxicities. Efficacy studies in a murine metastatic cancer model, demonstrated the ability to reduce the number and size of metastatic lesions. Methods: A First-in-Human open label dose escalation study was designed to evaluate the feasibility and safety of treatment in patients (n=18) with advanced metastatic solid tumors. A secondary objective was to evaluate initial efficacy signs. Eligibility criteria included patients with a life expectancy of at least 30 days with measurable disease according to RECIST 1.1. The patients underwent toxicity analysis and MRI scans without contrast media before (baseline), after treatment, and at the end of the follow-up period of 1 month. Vital signs were monitored before, during, and after treatment. Measurements included ECG, oral and body surface temperatures, blood pressure, heart rate, and oxygen saturation. Results: 3 patients were enrolled in the first cohort that received a single SaNP injection of 10% (first dose level) without AMF. No systemic toxicity was observed. 7 patients were then enrolled and SaNP was administered at the same dose followed by AMF irradiation (first dose level of 40%) of the torso area, conducted for two intervals of 5 min. each. SaNP administration procedures were successful in all cases whereas, 3 patients succeeded to complete the full treatment in accordance to the study protocol. During AMF exposure, the patients were covered with a cooling blanket and temperatures were monitored using fiber-optic sensors. There were no significant temperature deviations beside one patient, where a rise in oral temperature was noted due to the presence of dental implants which heated up. In all patients there were no significant differences in any of the vital signs post-injection nor before or after AMF except for one patient, for whom increased heart rate was observed during irradiation, returning to baseline thereafter. No treatment-related abnormal clinical pathology or urinalysis results were identified. Some fluctuations were observed, attributed to the disease stage. Although tumor response was not expected at the first dose levels, MRI and CT results for one patient showed a reduction in a breast tumor and in another patient, stable disease was reported. Conclusion: SaNP administration either alone or followed by AMF application was not associated with any significant adverse reactions, and no clinical or humoral toxicity was observed at initial doses of 10% SaNP and 40% AMF. Citation Format: Sarah Kraus, Cheri Tal, Boaz Shalev, Moshe Eltanani, Pazit Rukenstein, Shir Arbib, Michal Eck, Raz Khandadash, Shaul Atar, Arnoldo Cyjon, Ofer Shalev. Initial safety and feasibility results from a first-in-human clinical trial evaluating a novel magnetic hyperthermia approach for the treatment of metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT170.

Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

Both pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear. To compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer. This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The primary objective was to compare the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) between the two groups. Secondary objectives were to compare the disease control rate (DCR) and to analyze adverse events (AEs) between the two groups. A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab-combined chemotherapy group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P=0.634). The DCR was 92.10% and 92.10% in the sintilimab and pembrolizumab groups, respectively (P=0.991). The median PFS was 22.2 months for patients treated with sintilimab group compared with 16.5 months for patients treated with pembrolizumab group[hazard ratio (HR) = 0.743; 95% confidence interval (CI): 0.479-1.152; P = 0.599]. Patients treated with pembrolizumab did not achieve a median OS, and patients treated with sintilimab had a median OS of 30.7 months. In the sintilimab group, the incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63), and the incidence of grade 3-4 TRAEs of 42.9% (27/63). In the pembrolizumab group, the incidence of all TRAEs was 90.1% (91/101), and the incidence of grade 3-4 TRAEs was 37.6% (38/101). In the clinical treatment of Chinese patients with advanced squamous lung cancer, first-line treatment with sintilimab in combination with chemotherapy provided similar efficacy to pembrolizumab in combination with chemotherapy, and the treatment-related adverse effect profiles were comparable between the two groups, including similar rates of grade 3-4 and all adverse events.

Platelet-rich plasma in the treatment of alopecia areata: A retrospective evaluation of 17 patients

Background: Alopecia areata (AA) is a disease of unknown etiology which is thought to be autoimmune, that presents challenges in terms of treatment. Platelet-rich plasma (PRP) can induce the development of new hair follicles through various growth factors it contains. PRP could be a treatment option for patients with AA. Objectives: We aim to evaluate the effectiveness and safety of PRP treatment in patients with patch-type AA. Methods: The study included 17 patients diagnosed with patch-type AA who received PRP treatment at least 3 sessions every 4 weeks. Treatment response was evaluated by calculating the severity of alopecia tool (SALT) scores. Results: The mean age of patients was 29.70 ± 10.09, and the mean disease duration was 18.17 ± 39.46 months. The mean SALT score of 17 patients was 6.82 ± 4.96 and 4.35 ± 4.58 before treatment and at the end of the 3rd month, respectively. The reduction in SALT scores was statistically significant (P = 0.01). At the end of the 3rd month, six patients (35.3%) had an excellent response, one patient (5.9%) had a good response, one patient (5.9%) had a partial response, and nine patients (52.9%) showed no response. The mean SALT scores of four patients who received six sessions of PRP of treatment were 6.00 ± 2.94 and 1.75 ± 2.06 at the end of the 6th month. No serious side effects were noted. Relapse was observed in one patient within 1 year of follow-up. Conclusion: As a result of our study, PRP treatment was found to be an effective and reliable treatment method in patients with mild AA.

Endovascular treatment versus no endovascular treatment after 6–24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial

Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Outcomes of Endovascular Treatment for Posterior Circulation Stroke According to the Underlying Pathologic Mechanism: A Retrospective Single-Center Analysis

Objectives. This study investigated the functional outcomes and safety of endovascular treatment in patients with posterior circulation stroke according to whether the underlying mechanism was arterial embolism or intrinsic atherosclerosis. Materials and Methods. A total of 108 consecutive patients with posterior circulation ischemic stroke who received endovascular treatment between January 2018 and December 2021, 58 with arterial embolism and 50 with intrinsic atherosclerosis, were identified. The overall and basilar artery occlusion subgroup analyses were retrospectively conducted between the two study groups using a logistic regression model. Results. The rate of successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b–3) was comparable in the embolism versus intrinsic group (96.6% versus 90.0%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.01–42.74; P = 0.88 ). There was no significant difference in the frequency of a moderate outcome between the two groups (modified Rankin Scale [mRS] score 0–3: 43.1% versus 58.0%; aOR 0.63, 95% CI 0.15–2.50; P = 0.51 ), frequency of a favorable outcome (mRS 0–2: 39.7% versus 38.0%; aOR 1.59, 95% CI 0.37–6.70; P = 0.52 ), the 90-day mortality rate (34.5% versus 26.0%; aOR 2.31, 95% CI 0.50–10.63; P = 0.28 ), or frequency of symptomatic intracranial hemorrhage (6.9% versus 2.0%, respectively; P = 0.37 ). The subgroup analysis in patients with basilar artery occlusion found no significant between-group difference in any of the abovementioned clinical outcomes (all P &gt; 0.05 ). Conclusion. This study indicated that the mechanism of posterior circulation stroke had no significant effect on the functional outcomes after endovascular treatment or on procedural safety.

Anticoagulation for Atrial Fibrillation in Patients with Decompensated Liver Cirrhosis: Bold and Brave?

Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.

Abstract OT3-27-01: Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: a multicenter, phase 2, umbrella, FUTURE trial

Abstract Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes (luminal androgen receptor [LAR], immunomodulatory [IM], basal-like immune-suppressed [BLIS], mesenchymal-like [MES]) with distinct molecular features. We aimed to assess the efficacy and safety of molecular subtype-derived precision treatment in patients with heavily pretreated metastatic TNBC. Methods: This open-label, phase 2, umbrella trial included patients from four centers in China. Participants were women (aged ≥18 years) with histologically confirmed metastatic TNBC with disease progression after multiple lines of standard chemotherapy. Patients were enrolled into seven parallel arms according to their molecular subtypes: LAR with or without ERBB2 somatic mutation/amplification assigned to arm A (pyrotinib with capecitabine) and arm B (androgen inhibitor included therapy); IM assigned to arm C (anti-PD-1 antibody with nab-paclitaxel); BLIS with or without BRCA1/2 germline mutation assigned to arms D (PARP inhibitor included therapy) and E (anti-VEGFR included therapy); MES without or with PI3K-AKT mutation assigned to arms F (anti-VEGFR included therapy) and G (everolimus with nab-paclitaxel). Bayesian predictive probability was adopted to monitor each arm, which can be terminated independently according to a prespecified futility or efficacy boundary. This trial is registered with ClinicalTrials.gov, NCT03805399. Findings: Between October 18, 2018, and February 11, 2022, we enrolled 141 patients. All patients were heavily pretreated and resistant to six categories of the most common chemotherapeutic agents used in breast cancer treatment, with a median of 3 previous lines of therapies in the metastatic setting (Table 1 and 2). The median follow-up was 18.3 months (IQR 11.7-27.7). A confirmed objective response was achieved in 42 (29.8%, 95% CI 22.4-38.1) of the 141 patients. The median PFS was 3.4 months (95% CI 2.7-4.2), and the median OS was 10.7 months (95% CI 9.0-12.3) (Table 3). Arms A, C, E and G achieved efficacy boundaries, with 3 (75.0%) out of 4 patients in arm A, 20 (43.5%) out of 46 patients in arm C, 13 (28.3%) out of 46 patients in arm E, and 3 (33.3%) out of 9 patients in arm G achieving objective responses. Potential predictive biomarkers of efficacy in each arm were explored. Safety data were consistent with the known safety profiles of relevant drugs. Interpretation: We demonstrate the feasibility and clinical utility of a subtyping-based, genomic sequencing-guided strategy which allows the majority of heavily pretreated metastatic TNBCs to benefit from precision treatment. Most arms exhibit promising efficacy and manageable toxicities, providing subtyping schema to optimize personalized treatment. Table 1. The FUTURE trial schema. Patients are stratified into seven arms using the FUSCC 484-gene NGS panel testing and IHC subtyping. Abbreviations: mTNBC, metastatic triple-negative breast cancer; NGS, next-generation sequencing; IHC, immunohistochemistry; FUSCC, Fudan University Shanghai Cancer Center; LAR, luminal androgen receptor; IM, immunomodulatory; BLIS, basal-like immune-suppressed; MES, mesenchymal-like; n, number; AR, androgen receptor; PD-1, programmed cell death-1; PARPi, poly ADP-ribose polymerase inhibitor; VEGF, vascular endothelial growth factor; mTORi, mammalian target of rapamycin inhibitors. Table 2. Patient characteristics in the FUTURE trial. Table 3. Summary of treatment efficacy of TNBC in the FUTURE trial Citation Format: Zhi-Ming Shao, Zhong-Hua Wang, Yi-Zhou Jiang, Yin Liu, Xiu-Zhi Zhu, Yi Xiao, Song-Yang Wu, Wen-Jia Zuo, Qiang Yu, A-Yong Cao, Jun-Jie Li, Ke-Da Yu, Guang-Yu Liu, Jiong Wu, Tao Sun, Jiuwei Cui, Zheng Lv, Hui-Ping Li, Xiao-Yu Zhu. Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: a multicenter, phase 2, umbrella, FUTURE trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-27-01.

High-flow nasal cannula for severe COVID-19 patients in a Japanese single-center, retrospective, observational study: 1 year of clinical experience.

High-flow nasal cannula (HFNC) can be effective in treating type 1 respiratory failure by reducing the severity of coronavirus disease 2019 (COVID-19). The purpose of this study was to assess the reduction of disease severity and safety of HFNC treatment in patients with severe COVID-19. We retrospectively observed 513 consecutive patients with COVID-19 admitted to our hospital from January 2020 to January 2021. We included patients with severe COVID-19 who received HFNC for their deteriorating respiratory status. HFNC success was defined as improvement in respiratory status after HFNC and transfer to conventional oxygen therapy, while HFNC failure was defined as transfer to non-invasive positive pressure ventilation or ventilator, or death after HFNC. Predictive factors associated with failure to prevent severe disease were identified. Thirty-eight patients received HFNC. Twenty-five (65.8%) patients were classified in the HFNC success group. In the univariate analysis, age, history of chronic kidney disease (CKD), non-respiratory sequential organ failure assessment (SOFA) ≥ 1, oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) before HFNC ≤ 169.2, were significant predictors of HFNC failure. Multivariate analysis revealed that SpO2/FiO2 value before HFNC ≤ 169.2 was an independent predictor of HFNC failure. No apparent nosocomial infection occurred during the study period. Appropriate use of HFNC for acute respiratory failure caused by COVID-19 can reduce the severity of severe disease without causing nosocomial infection. Age, history of CKD, non-respiratory SOFA before HFNC ≤ 1, and SpO2/FiO2 before HFNC ≤ 169.2 were associated with HFNC failure.

Kampo medicine for COVID‐19 prevention, treatment, and recovery in clinical and pharmacological aspect

Kampo medicine for <scp>COVID</scp>‐19 prevention, treatment, and recovery in clinical and pharmacological aspect

Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non-small cell cancer: A systematic review and network meta-analysis.

This study compares the safety and efficacy of first-line treatments for anaplastic lymphoma kinase (ALK)-mutated non-small cell lung cancer (NSCLC). A comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Abstracts related to lung cancer presented at important international conferences were also reviewed. Randomized clinical trials that qualified the inclusion criteriawere subjected to Bayesian network meta-analysis and systematically reviewed. The authors included a total of nine studies including 2441 patients and seven first-line treatments (ensartinib, brigatinib, crizotinib, lorlatinib, alectinib, ceritinib, and pemetrexed-based chemotherapy). Overall, lorlatinib appeared to confer the best progression-free survival (PFS) (probability of being the best [Prbest], 90%; surface under the cumulative ranking curve [SUCRA], 98%), and the same conclusion was obtained on paired comparisons (lorlatinib vs. ceritinib [hazard ratio (HR), 0.31; 95% confidence interval (CI), 0.20-0.47); lorlatinib vs. chemotherapy [HR, 0.17; 95% CI, 0.12-0.23]; crizotinib vs. lorlatinib [HR, 3.6; 95% CI, 2.4-5.2]; and brigatinib vs. lorlatinib [HR, 1.7; 95% CI, 1.0-2.8]). Alectinib conferred the best overall survival (OS) and safety profile. In the Asian population, ensartinib conferred the best PFS (Prbest 50%, SUCRA 87%), and for patients with brain metastases at baseline, lorlatinib showed the best PFS (Prbest 70%, SUCRA 93%). For first-line treatment of patients with ALK-positive NSCLC, lorlatinib was associated with the best PFS and objective response rate, but poorer safety profile, whereas alectinib demonstrated the best OS and safety profile. In Asians, ensartinib conferred the best PFS benefit, and in the brain baseline metastasis population, lorlatinib conferred the best PFS benefit. Among the many molecularly targeted drugs currently used to treat anaplastic lymphoma kinase mutation-positive non-small cell lung cancer, lorlatinib may be one of the most effective targeted drugs. Lung cancer has long been at the top of cancer rankings in terms of incidence and mortality. Today, the treatment of lung cancer has moved into the era of precision therapy. In this article, we use a statistical approach to compare the efficacy and safety of targeted drugs that have been used in the first-line treatment of anaplastic lymphoma kinase mutations to improve the reference for clinicians to make treatment decisions in the real world.

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis.

Dual-targeting chimeric antigen receptor (CAR)-T cell therapy has been proposed as a potential solution for overcoming antigen escape during anti-CD19 CAR-T treatment. We performed this systematic review and meta-analysis to investigate the efficacy and safety of this novel treatment in patients with B cell non-Hodgkin lymphoma (B-NHL) and B cell acute lymphoblastic leukemia (B-ALL). We systematically searched relevant literature based on databases (PubMed, Web of Science, Embase and Cochrane) and conference abstracts. The primary outcomes measured were the best objective response rate (ORR) or complete response (CR), 12-month overall survival (OS) and progression-free survival (PFS), cytokine release syndrome (CRS), and neurotoxicity. Fifteen registered prospective open-label clinical trials were included. Among the 260 patients with B-NHL, the pooled best ORR and CR were 77% (95% confidence interval [CI]: 0.71-0.82) and 52% (95% CI: 0.40-0.63), respectively, and the pooled 12-month PFS and OS were 54.0% (95% CI: 0.47-0.61) and 66.0% (95% CI: 0.56-0.77), respectively. In the 159 patients with B-ALL, the combined best CR was observed to be 92% (95% CI: 0.82-0.99) and the pooled 12-month PFS and OS were 65.0% (95% CI: 0.51-0.77) and 73.0% (95% CI: 0.56-0.92), respectively. Moreover, in B-NHL patients, grade ≥3 CRS was observed in 14.0% (95% CI: 0.04-0.29) of these patients, and 5.0% (95% CI: 0.02-0.08) showed grade ≥3 neurotoxicity; in the case of B-ALL patients, grade ≥3 CRS and neurotoxicity occurred in 11.0% (95% CI: 0.04-0.19) and 2.0% (95% CI: 0.00-0.06), respectively. This study demonstrates the safety and clinical efficacy of dual-targeting CAR-T cell therapies in B cell malignancies. Further, well-designed randomized controlled trials are required to establish the role of dual-targeting CAR-T cell therapy in patients with B cell malignancies.

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study.

Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

Preliminary Clinical Study of the Effects and Safety of 308-nm Excimer Light Treatment in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a common skin disease which, depending on its severity, can have a significant impact on the quality of life of affected individuals. In cases of severe AD, systemic immunomodulatory agents can be considered for treatment. However, the available treatment options for moderate AD are limited. According to previous reports, however, 308-nm excimer light is a potential treatment for localized, moderate AD. This study aimed to assess the clinical efficacy and safety of 308-nm excimer light in Korean adults with AD. This study included Korean patients aged over 19 years, who were diagnosed with AD by a dermatologist, with bilateral, symmetric, and eczematous lesions. The symmetrical lesions in each patient were treated as control-test pairs. Treatment with 308-nm excimer light was applied to the test lesion twice a week for 4 weeks. The severity of the eczema, trans-epidermal water loss, and epidermal capacitance were measured. A total of 25 participants were enrolled in the study. After the first visit, two participants withdrew, whereas the remaining 23 completed the study. There was a statistically significant improvement in AD severity in the test group than in the control group (p<0.001). Skin barrier function also improved in the test than in the control group (p<0.01). This study provides preliminary evidence for the use of 308-nm excimer light as a treatment option to improve symptoms and skin barrier function in moderately localized AD.

P197: Long term efficacy and safety of carglumic acid treatment in patients with organic acidemia in East Asia population

P197: Long term efficacy and safety of carglumic acid treatment in patients with organic acidemia in East Asia population

Efficiency and Reliability of Bronchoscopic Lung Volume Reduction Coil Application in Patients with Severe Emphysema.

In the past years, surgery has been used for the non-medical treatment of severe emphysema. However, in recent years, bronchoscopic lung volume reduction (LVR) treatment has become more preferred because it is less invasive. Bronchoscopic coil treatment is the most frequently applied technique among these methods. The aim of the investigation was to determine the efficacy and safety of bronchoscopic volume reduction coil treatment for patients with severe emphysema. The patients who were performed bronchial volume reduction coil treatment between 2015 and 2017 and were followed in our outpatient clinic were retrospectively examined. They were followed for 1 year at quarterly intervals after the procedure. All the safety and efficacy of the patient's records, including the modified Medical Research Council (MRC) dyspnea score, the St. George's Respiratory Questionnaire (SGRQ) quality of life scale, the 6 min walk distance (6-MWT), pulmonary function tests, and adverse events, were evaluated. Sixteen patients were included in the study. The mean of the preoperative mMRC clinic dyspnea score was 3.38, the mean of the 3rd month's mMRC score was 2.62 (p=0.007), and the mean of the 12th month's mMRC was 2.37 (p=0.003). The preoperative SGRQ quality of life parameter was 71.95±15.7, the 3rd month was 66.7±16.2 (p=0.007), and the 12th month was 62.9±16.4 (p=0.003). Preoperative mean of 6-MWT was 247.25±112.36 m, 3rd month 264.25±95 m (p=0.148), and 12th month 317±122.9 m (p=0.034). Patients' preoperative residual volume was 5.28±1.96 L, 3rd month 4.52±1.35 L (p=0.023), and 12th month 4.545±1.83 L (p=0.163). Patients' preoperative forced expiratory volume in one second, respectively, was 0.79±0.29 L, 3rd month 0.79±0.3 L (p=0.917), and 12th month 0.86±0.3 L (p=0.756). It seems that bronchoscopic LVR coil treatment, which is an effective and reliable procedure that reduces shortness of breath rather than respiratory function test parameters and improves the quality of daily life, will become even more widespread.