Multicenter Real-world Study Research Articles

Abstract P1-14-03: Efficacy and safety of pyrotinib-based therapy in the treatment of HER2-positive breast cancer patients with brain metastases:a multi-center real-world study

Abstract Background: An estimated 30-50% of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), and there are few effective treatment options. Pyrotinib has shown good efficacy in HER2-positive breast cancer patients with BMs in a single-arm phase II trial, but there is a lack of data from randomized controlled trial and real-world study. The purpose of this multi-center real-world study was to evaluate the efficacy and safety of pyrotinib-based therapy in HER2-positive breast cancer patients with BMs in real world. Methods: We reviewed the data of HER2-positive breast cancer patients with BMs who were treated with pyrotinib-based therapy from January 2018 to September 2021 at Shandong Cancer Hospital and Institute and other hospitals in Shandong Province in China. The initial dose of pyrotinib in most patients (n=92, 85.2%) was 400 mg once a day for every 21 days as a cycle. All patients were evaluated for tumor response every two cycles according to RECIST 1.1. The primary endpoint was progression free survival (PFS) and secondary endpoints were compounded objective response rate (ORR) and CNS-ORR (the ORR of central nervous system), compounded disease control rate (DCR) and CNS-DCR (the DCR of central nervous system) and overall survival (OS). The safety profile has also been assessed. The updated graded prognostic assessment for breast cancer patients with brain metastases (Breast GPA) includes age, Karnofsky performance status (KPS), extracranial metastases, number of brain metastases, and tumor subtype. It is divided into four subgroups (0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0) with different prognosis (the median survival: 6 months, 12.9 months, 23.5 months, and 36.3 months). Results: 101 patients were assessed for efficacy and toxicity. The median PFS is 10.0 months (95% CI, 6.9 to 13.1 months), and OS data were not available at the time of analysis. In overall patients, patients with GPA of 0-2.0 achieved shorter PFS (4.8 months vs 12.4 months, P=0.003). Trastuzumab (neo and adjuvant) (P=0.021), local therapy for BMs (P﹤0.001) and pyrotinib treatment (P=0.022) had significant positive correlation with PFS. In patients with GPA of 0-2.0, the median PFS of different local treatment methods was significantly different (P﹤0.001), stereotactic radiotherapy alone (13.6 months) was better than whole-brain radiotherapy alone (4.8 months) and combined local therapy (6.7 months); patients who received pyrotinib first in the BMs stage had longer PFS than those who did not (6.7 months vs 2.7 months, P=0.009) and radiotherapy for BMs (P=0.036) had correlation with longer PFS. Cox multivariate analysis indicated that GPA (0-2.0 vs 2.5-4.0) was independent predictor of PFS. For overall patients, the ORR was 42.6% and DCR was 88.1%. The CNS-ORR was 45.5% and CNS-DCR was 90.1%. Diarrhea (71.3%) was the most common adverse events (AEs), 47 patients (46.5%) reported grade 1-2 diarrhea, 25 patients (24.8%) reported grade 3 diarrhea. In addition, the more common AEs of grade 3 were loss of appetite (7.9%), hand-foot syndrome (6.9%), nausea (5.9%) and vomiting (5.0%). No grade 4 and 5 AEs occurred. Conclusions: Pyrotinib-based therapy is effective and tolerable in HER2-positive breast cancer patients with BMs. In the subgroup with Breast GPA 0-2.0, patients treated with radiotherapy had a better prognosis, and stereotactic radiosurgery alone was a viable option. Clinical trial information: ChiCTR2000037995. Citation Format: Huihui Li, Jie Huang, Qiaorui Tan, Xiaochu Man, Sha Yin, Shujuan Sun, Yu Hu, Wenhuan Li, Dongdong Zhou, Lihua Song, Baoxuan Zhang, Liang Xu, Xinzhao Wang, Xuemei Xie. Efficacy and safety of pyrotinib-based therapy in the treatment of HER2-positive breast cancer patients with brain metastases:a multi-center real-world study [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 P1-14-03.

Abstract P1-11-18: The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China

Abstract Background: Dual HER2 targeted therapy with trastuzumab (H) and pertuzumab (P) has been approved as neoadjuvant therapy for patients with HER2-positive breast cancer in China in 2019 based on the results from NeoSphere and PEONY study. However, the real-world efficacy and safety data are currently lack of evidence in China. Therefore, this multi-center real-world study aims to retrospectively analyze the efficacy and safety of neoadjuvant trastuzumab and pertuzumab combined with different chemotherapy regimens of HER2-positive early breast cancer. Methods: Patients received trastuzumab and pertuzumab in combination with different chemotherapy regimens, including taxanes (T), cyclophosphamide (C), anthracyclines (A) were collected retrospectively from 12 centers. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Results: A total of 357 patients were enrolled, among which 204 (57.5%) recieved TCbHP, 92 (25.9%) recieved EC-THP, and 51 (14.4%) received THP as chemotherapy regimens. The median age was 48 years old (range, 22-76), 142 (39.8%) of patients were classified as hormone receptor (HR)-positive, and 215 (60.2%) were HR-negative. The overall tpCR rate was 58.5% (95%CI, 53.2%-63.7%). tpCR rate for HR-negative patients was significantly higher than HR-positive patients (65.6% vs. 47.9%, p=0.001) and there was not any statistical difference according to chemotherapy regimens (56.9% for TCbHP, 56.5% for EC-THP, and 66.7% for THP, p=0.445). The most common adverse events included anemia (40.1%), white blood cell count decreased (34.3%), ejection fraction decreased (19.5%), Alanine aminotransferase increased (18.9%), platelet count decreased (12.8%) and neutrophil count decreased (12.0%). There was not any toxicity leading to death. Conclusions: Multi-center real-world data show satisfactory tpCR rate and tolerable adverse events of trastuzumab and pertuzumab in combination with different chemotherapy regimens in China. Citation Format: Xiaowei Qi, Hong Hu, chen wenlin, xu yan, liu shu, fang yanman, Taolang Li, ming jia, zhou sihai, chai fan, liang yueyang, fan yuanming, Yi Zhang, Peng Tang, jiang jun, nie jianyun, Li Chen, Shushu Wang. The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China [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 P1-11-18.

A chemotherapy-free regimen improves prognosis in elderly diffuse large B-cell lymphoma patients with a low-performance status score: A Chinese multi-center real-world study.

Because patients with diffuse large B-cell lymphoma (DLBCL) aged >80 years old typically experience dismal outcomes, it is essential to improve disease control and reduce side effects in such patients. This was a multi-center retrospective study. Patients aged ≥80 years with pathologically confirmed DLBCL were treated in four centers in the Guangdong province between January 2010 and November 2020. Clinical data from patients receiving different treatment modalities were extracted from electronic medical records. Finally, 50 patients aged ≥80 years were included; four (8.0%) refused treatment, 19 (38%) patients belonged to the chemotherapy-free group, and 27 (54%) patients were in the chemotherapy group. Patients receiving chemotherapy-free treatment had more often a non-germinal center B phenotype than those treated with chemotherapy (P = 0.006). The median progression-free survival (PFS) in the chemotherapy-free group was longer than that in the chemotherapy group (24.7 vs 6.3 months, P = 0.033). Good performance status (PS <2) was associated with higher PFS and overall survival (OS) (P = 0.03; P = 0.02, respectively). In patients with PS of ≥2, the median PFS and OS did not differ between the chemotherapy-free and chemotherapy groups (P = 0.391; P = 0.911, respectively). After stratifying patients with PS <2, the PFS and OS of the chemotherapy-free group were better than those of the chemotherapy group (58.1 vs 7.7 months, P = 0.006; 58.1 vs 26.5 months, P = 0.050). However, treatment-related toxicity did not differ between groups. PS was an independent prognostic factor of elderly DLBCL patients. Accordingly, patients aged ≥80 years with a PS of <2 could benefit from a chemotherapy-free regimen.

Nutrition impact symptoms: Noteworthy prognostic indicators for lung cancer

Nutrition impact symptoms (NIS) in head and neck cancer are well-studied and are found to be heavy contributors of poor outcome. However, the prevalence and role of NIS in other cancer are less addressed. In this study, we investigated the incidence and prognostic role of NIS in patients with lung cancer. NIS, evaluated by patient-generated subjective global assessment (PG-SGA) in a multicenter real-world prospective study, included loss of appetite, nausea, vomiting, mouth ulcer, constipation, diarrhea, dry mouth, taste change, altered smell, dysphagia, early satiety, and pain. The endpoints were the patients' overall survival (OS) and quality of life (QoL). The COX analysis was used to investigate the relationship between NIS and OS. Interaction analysis and mediation analysis were performed to determine the modifiers and mediator. 3634 patients with lung cancer were enrolled in this study, of which 1533 patients had NIS. During the average follow-up of 22.65 months, 1875 deaths occurred. The OS of patients with lung cancer with NIS was lower than that of patients without NIS. NIS (HR, 1.181, 95% CI, 1.073-1.748), loss of appetite (HR, 1.266, 95% CI, 1.137-1.409), vomiting (HR, 1.282, 95% CI, 1.053-1.561), and dysphagia (HR, 1.401, 95% CI, 1.079-1.819) were independent prognostic factors in patients with lung cancer. There were interactions between chemotherapy and primary tumor on NIS . In the relationship between different types of NIS (NIS, loss of appetite, vomiting, dysphagia) and prognosis, the mediating effects of inflammation accounted for 15.76%, 16.49%, 26.32%, and 18.13%, respectively. Meanwhile, these three NIS were closely associated with the occurrence of severe malnutrition and cancer cachexia. 42% patients with lung cancer experienced different types of NIS. NIS were independent indicators of malnutrition, cancer cachexia and shorter OS, and closely related to QoL. NIS management is of clinical significance.

Anlotinib plus PD-1 inhibitors as chemo-free therapy in advanced or metastatic esophageal cancer: Updated results from a retrospective real-world study.

310 Background: Compared to standard chemotherapy, immune checkpoint inhibitors monotherapy and combined with chemotherapy regimens have been shown significant benefits for patients with advanced or metastatic esophageal cancer in both second-line and first-line treatment, respectively. Anlotinib was an effective second-line monotherapy for esophageal squamous cell carcinoma in China and the combination of anlotinib and immunotherapy might be a promising strategy. The study aimed to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors during the treatment of esophageal cancer in the real world setting. Methods: This is a multicenter real-world study in patients with unresectable locally advanced, recurrent or metastatic esophageal cancer, who would benefit from anlotinib plus a PD-1 inhibitor under the doctor's evaluation. The enrolled patients received treatment according to physicians. The primary endpoint was PFS, and secondary endpoints included ORR, DCR and OS. The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Sep 2022, 207 pts were enrolled. 109 comprised the evaluable population. In the full analysis set, 203 patients were squamous cell and 4 were adenocarcinoma histology. 137 of 207 (66.2%) pts were male. 44(21.3%) had an ECOG performance status of 0, 136 (65.7%) status of 1 and 27 (13.0%) status of ≥2. 47 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 8 cases had combined anti-PD-1/PD-L1 antibody and vascular targeting drugs. Among the 109 evaluable pts, 17 (15.6%) pts received first-line therapy, 64 (58.7%) second-line and 28(25.7%) third &amp; above line. Of which, 5 patients achieved complete response (CR), 32 pts partial response (PR), 62 pts stable disease (SD), illustrating an ORR of 34.0% (95%CI 25.1-43.6) and a DCR of 90.8%(95%CI 83.8-95.5). In the first line therapy, ORR was 47.1% and DCR was 88.2%. In the second line therapy, ORR was 32.8% and DCR was 96.9%. In the third &amp; above line, ORR with 28.6% and DCR with 78.6% were observed. Median PFS was not reached, 6m-PFS rate was 87.9%. Treatment related adverse events (TRAEs) were reported in 55 pts (50.5%). 6 patients had grade 3 or more TRAEs. Conclusions: Anlotinib plus PD-1 inhibitors for advanced or metastatic esophageal cancer demonstrated a promising clinical benefit and a manageable safety profile. Further investigation in larger cohorts and even randomized controlled studies is warranted. Clinical trial information: NCT04966611 .

Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China

BackgroundReal-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China.MethodsHR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test.ResultsIn total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation.ConclusionPalbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 − MBC.

P734 A single measurement of fecal calprotectin, particularly if combined with hemoglobin and C-reactive protein levels, predicts Crohn’s disease prognosis - a prospective study

Abstract Background Early flare prediction is essential for the timely management of Crohn’s disease (CD) patients, allowing to optimize the available therapeutic toolbox and to decrease the disease burden. We aimed to evaluate the performance of readily available biomarkers (when evaluated at least once or more frequently during follow-up) and to develop risk matrices to predict CD progression. Methods CD patients receiving infliximab (IFX) as maintenance therapy (n=289) were followed up for 24 months; those patients were enrolled in DIRECT, a prospective, multicenter real-world study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including also IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. Results The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p≤0.001] for composite outcomes 1 and 2, respectively), regardless of confounding factors. Levels of C-reactive protein (CRP) above 10.0 mg/L or fecal calprotectin (FC) above 500.0 µg/g, in at least one visit, were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when found in at least two visits (consecutive or not). The risk matrices combining the different non-invasive biomarkers had a good ability to predict CD progression. Indeed, patients simultaneously presenting anemia, CRP&amp;gt;10 mg/dL and FC&amp;gt;500.0 µg/g at least once had a probability of disease progression that ranged between 42 and 63%. Conclusion The combined evaluation of FC, hemoglobin, and CRP in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making. This is one of the first studies developing risk matrices to predict the occurrence of composite outcomes in CD patients, providing an easily applicable tool for CD clinical management.

P278 Endoscopic scoring system utilization for Inflammatory Bowel Disease activity assessment: a multicenter real-world evidence study from Argentina (DARE study)

Abstract Background The use of scores for the assessment of endoscopic activity in inflammatory bowel disease (IBD) patients is crucial for accurate and reproducible evaluation of mucosal healing, which is a relevant marker of prognosis. Frequency and patterns of their use in a real-life setting are not known. We aimed to describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. Methods A multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn’s disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between July 2018 and July 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We compared the endoscopic findings to determine if there were differences in the score reported and the inflammatory activity described. Finally, we determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist’s specialty, years of experience as well as expertise in IBD were assessed. Chi square test was used for the comparison of categorical variables; Student t test for the comparison of numerical variables. A multivariate analysis was performed using a logistic regression model. A p value of less than 0.05 was considered to be statistically significant. Results A total of 1206 patients were included for analysis (32.25% patients with Crohn’s disease). Mean age was 45.48±15.6. Endoscopic score reporting was found in only 34.45% of Crohn’s disease colonoscopies and in 52.87% of ulcerative colitis colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%). We found discrepancies between the score reported and the findings described in colonoscopies in 10.92% of cases; only 26% of reports included all recommendations proposed by BRIDGe group. On multivariate analysis, surgeons as operators [OR 0.08 (0.03-0.18)], &amp;gt;15 years of endoscopist experience [OR 0.24 (0.07-0.37)], IBD expertise [OR 2.86 (1.86-4.41)] and compliance of quality elements of reporting [OR 2.48 (1.24-3.76)] were significantly associated with endoscopic score reporting. Conclusion We identified a low prevalence of endoscopic activity score reporting in IBD patients’ colonoscopies. This finding is associated with operator-dependent characteristics. Educational interventions can be introduced to increase adequate score reporting.

Early oral feeding following intestinal anastomosis surgery in infants: a multicenter real world study.

To prevent postoperative complications, delayed oral feeding (DOF) remains a common model of care following pediatric intestinal anastomosis surgery; however, early oral feeding (EOF) has been shown to be safe and effective in reducing the incidence of complications and fast recovery after pediatric surgery. Unfortunately, the evidence in support of EOF after intestinal anastomosis (IA) in infants is insufficient. Therefore, this study was primarily designed to evaluate the safety and efficacy of EOF. In addition, the current status of EOF application and associated factors that favor or deter EOF implementation were also assessed. A total of 898 infants were divided into two groups (EOF group, n = 182; DOF group, n = 716), and the clinical characteristics were collected to identify the factors associated with EOF in infants. Complications and recovery were also compared to define the safety and efficacy after balancing the baseline data by propensity score matching (PSM) (EOF group, n = 179; DOF group, n = 319). The total EOF rate in infants with IA was 20.3%. Multivariate logistic regression revealed significant differences in the EOF rates based on IA site and weight at the time of surgery (OR = 0.652, 95% CI: 0.542-0.784, p < 0.001) and (OR = 1.188, 95% CI: 1.036-1.362, p = 0.013), respectively. The duration of total parenteral nutrition (TPN), parenteral nutrition (PN), and postoperative hospital stay were significantly shorter in the EOF group than the DOF group [2.0 (1.0, 2.0) d vs. 5.0 (3.0, 6.0) d; 6.0 (5.0, 8.0) d vs. 8.0 (6.0, 11.0) d; 10.0 (7.0, 14.0) d vs. 12.0 (9.0, 15.0) d, all p < 0.001]. The rates of abdominal distension and vomiting in the EOF group were significantly higher than the DOF group (17.9% vs. 7.2%, p < 0.001; 7.8% vs. 2.5%, p = 0.006); however, no differences were found in failure to initial OF, diarrhea, hematochezia, and anastomotic leakage between the two groups (p > 0.05). The overall rate of EOF in infants following IA was low, and the sites of anastomosis and weight at surgery were two factors associated with EOF. Nevertheless, performing EOF in infants after IA was safe and effective, reduced PN usage, shortened the hospital stay, and did not increase the rate of severe complications.Clinical Trial Registration: ClinicalTrails.gov, identifier NCT04464057.

Beyond atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: overall efficacy and safety of tyrosine kinase inhibitors in a real-world setting.

In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapeutic sequence is still unclear and no second-line agent has proven its efficacy. The aim of this retrospective multicenter real-world cohort study was to provide an evaluation of the efficacy and safety of the use of second-line tyrosine kinase inhibitors (TKIs) in this population. All patients with advanced HCC, treated in first-line setting by atezolizumab-bevacizumab, and who received at least one dose of treatment with TKI were included in this study. All the data were retrospectively collected from medical records. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall global survival (OGS), and safety. A total of 82 patients were included in this study. Patients were assigned to the regorafenib group (n = 29, 35.4%) or other TKI (sorafenib n = 41, lenvatinib n = 8, or cabozantinib n = 4) group (n = 53). PFS was not significantly different between the two groups [2.6 versus 2.8 months, HR 1.07 (95% CI: 0.61-1.86), p = 0.818]. Median PFS rates were 2.6, 4.4, and 2.8 months in sorafenib-, lenvatinib-, and cabozantinib group, respectively. OS was statistically different between the regorafenib group and other TKI group [15.8 versus 7.0 months, HR 0.40 (95% CI: 0.20-0.79), p = 0.023]. When adjusting on confounding factors, there was still a difference in OS favoring the regorafenib group (adjusted hazard ratio 0.35, p = 0.019). OGS of patients who received regorafenib was improved compared to other TKI [18.6 versus 15.0 months, HR 0.42 (95% CI: 0.22-0.84), p = 0.036]. Twenty percent of patients had grade 3 and none had grade 4 or 5 adverse events. In patients who experienced disease progression and fit for a third-line treatment, 80% and 50% received cabozantinib in regorafenib group and other TKI group, respectively. Efficacy of any TKI in the second-line setting was not affected by atezolizumab-bevacizumab treatment as first-line therapy. The safety profile in the second-line setting was consistent with the results shown in pivotal studies. PFS rates of patients were similar, regardless of TKI type. Regorafenib was associated with better OS and OGS rates compared to other TKI. These data need to be confirmed in prospective comparative studies.

Real-World Study on Chai-Shi-Jie-Du Granules for the Treatment of Dengue Fever and the Possible Mechanisms Based on Network Pharmacology.

Traditional Chinese medicine (TCM) is a widely used method for treating dengue fever in China. TCM improves the symptoms of patients with dengue, but there is no standard TCM prescription for dengue fever. This real-world study aimed to evaluate the effects of Chai-Shi-Jie-Du (CSJD) granules for the treatment of dengue fever and the underlying mechanisms. We implemented a multicenter real-world study, an in vitro assay and network pharmacology analysis. Patients from 5 hospitals in mainland China who received supportive western treatment in the absence or presence of CSJD were assigned to the control and CSJD groups between 1 August and 31 December 2019. Propensity score matching (PSM) was performed to correct for biases between groups. The clinical data were compared and analyzed. The antidengue virus activity of CSJD was tested in Syrian baby hamster kidney (BHK) cells using the DENV2-NGC strain. Network pharmacological approaches along with active compound screening, target prediction, and GO and KEGG enrichment analyses were used to explore the underlying molecular mechanisms. 137 pairs of patients were successfully matched according to age, sex, and the time from onset to presentation. The time to defervescence (1.7 days vs. 2.5 days, P < 0.05) and the disease course (4.1 days vs. 6.1 days, P < 0.05) were significantly shorter in the CSJD group than those in the control group. CSJD showed no anti-DENV2-NGC virus activity in BHK cells. Network pharmacology analysis revealed 108 potential therapeutic targets, and the top GO and KEGG terms were related to immunity, oxidative stress response, and the response to lipopolysaccharide. CSJD granules exhibit high potential for the treatment of dengue fever, and the therapeutic mechanisms involved could be related to regulating immunity, moderating the oxidative stress response, and the response to lipopolysaccharide.

Comparative Effectiveness of Apixaban and Rivaroxaban Lead-in Dosing in VTE Treatment: Observational Multicenter Real-World Study

Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen.

Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study.

The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child-Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400ng/mL, presence of extrahepatic disease, albumin-bilirubin (ALBI) grade 2, and no previous locoregional procedures. Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR.

Ferric Carboxymaltose in the Management of Iron Deficiency Anemia in Pregnancy: A Subgroup Analysis of a Multicenter Real-World Study Involving 1191 Pregnant Women.

Real-world evidence of the efficacy and safety of ferric carboxymaltose (FCM) infusion in Indian pregnant women with iron deficiency anemia (IDA) is lacking. To assess the efficacy and safety of intravenous (IV) FCM in Indian pregnant women with IDA in 4 weeks in a real-life scenario. This is a subgroup analysis of our previously conducted retrospective, multicenter, observational, real-world PROMISE study. Data on demographic and hematological parameters, patient-reported adverse events, and physicians' clinical impressions of efficacy and safety were analysed at 4 ± 1 week. This subgroup analysis included 1191 pregnant women in whom IV FCM resulted in a significant increase in hemoglobin (Hb) by 2.8 g/dL and serum ferritin by 30.03 μg/L at 4 weeks (P < 0.001 for both). In 103 pregnant women with severe IDA, there was a significant increase in Hb by 3.6 g/dL (P < 0.001), and serum ferritin by 16.96 μg/L (P=0.12). In 978 pregnant women with moderate IDA, significant improvement in Hb by 2.74 g/dL and serum ferritin by 33 μg/L (P < 0.001 for both) was noted. Similarly, there was a significant increase in red blood cell count, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin (P < 0.001 for all). In pregnant women with mild IDA (n = 26), Hb increased significantly by 1.99 g/dL (P < 0.001). Adverse effects were reported in 8.6% of pregnant women. No new safety signals or serious adverse effects were observed. Based on physicians' global assessment, good to very good efficacy and safety of IV FCM was noted in 99.2% and 98.6% of pregnant women, respectively. IV FCM rapidly corrected anemia in a short period of 4 weeks with favorable safety in the second and third trimester of pregnancy with all severities of IDA (severe, moderate, and mild). The physicians' favorable global assessment of FCM's efficacy and safety in pregnant women with IDA supports its use in daily clinical practice. This trial is registered with CTRI/2021/12/039065.

Survival in Breast Cancer Patients with Bone Metastasis: A Multicenter Real-World Study on the Prognostic Impact of Intensive Postoperative Bone Scan after Initial Diagnosis of Breast Cancer (CSBrS-023).

The prognostic value of intensive postoperative bone scan (BS) screening, which is performed in asymptomatic patients with breast cancer (BC) after surgery, remained unclear. Patients diagnosed with BC with bone metastasis (BM) from five medical centers in China during the years 2005−2013 were retrospectively collected. Propensity score matching (PSM) was performed to balance the baseline characteristics. The survival outcomes were overall survival (OS) and overall survival after BM (OSABM). Among 1059 eligible patients, 304 underwent intensive postoperative BS while 755 did not. During a median follow-up of 6.67 years (95%CI 6.45, 7.21), intensive postoperative BS prolonged the median OS by 1.63 years (Log-Rank p = 0.006) and OSABM by 0.66 years (Log-Rank p = 0.002). Intensive postoperative BS was an independent prognostic factor for both OS (adjusted HR 0.77, 95%CI 0.64, 0.93, adjusted p = 0.006) and OSABM (adjusted HR 0.71, 95%CI 0.60, 0.86, adjusted p < 0.001). The prognostic value of intensive postoperative BS was consistently favorable for OS among clinical high-risk patients, including those with ages younger than 50, stage II, histology grade G3 and ER-Her2- subtype. This multicenter real-world study showed that intensive postoperative BS screening improved survival for BC patients with BM and should probably be recommended for postoperative surveillance, especially for patients at clinical high-risk.

A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia

BackgroundThe real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations.MethodsThis was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up.ResultsData from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy.ConclusionsAlthough patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice.

Tailoring second-line or above therapy for patients with advanced or metastatic gastric cancer: A multicenter real-world study.

Background: There is currently still a lack of effective therapeutic manner after the failure of first-line therapy for patients with advanced or metastatic gastric cancer. The present study aimed to evaluate the clinical efficacy and safety of different treatment strategies as second-line or above therapy for patients with advanced or metastatic gastric cancer. Methods: This was an observational multicenter real-world study. From January 2018 to December 2020, advanced or metastatic gastric cancer patients who have failed prior therapy were enrolled and treated with chemotherapy, anti-angiogenic TKIs (tyrosine kinase inhibitors) + chemotherapy or TKIs + ICIs (immune checkpoint inhibitors). In this study, progression free survival (PFS) was the primary end-point. Other evaluation indicators were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and drug toxicities. Results: 162 patients were enrolled, of which 61 patients received chemotherapy, 47 patients received TKIs plus chemotherapy, and 54 patients received TKIs + ICIs. No statistically significant difference existed in ORR among groups (16.4% vs. 19.1% vs. 18.5%, p = 0.924). Patients who received TKIs plus chemotherapy obtained better DCR compared with the chemotherapy group (78.7% vs. 54.1%, p = 0.008), and simultaneously, the median PFS (3.3m vs. 2.8m, p = 0.001) and OS (8.0m vs. 5.8m, p = 0.005) in TKIs plus chemotherapy group were superior to chemotherapy group. Consistent results were observed in subgroup analysis, including sex, age, ECOG, number of metastatic sites and treatment line. No statistically differences were found between TKIs + ICIs and the chemotherapy group concerning DCR (63.0% vs. 54.1%, p = 0.336), median PFS (3.0m vs. 2.8m, p = 0.051) and OS (5.2m vs. 5.8m, p = 0.260). Different treatment manner present a special spectrum of adverse events (AEs), and the incidence of Grade 3-4 AEs were 31.1%, 38.3% and 18.5%, respectively. Conclusion: Compared with chemotherapy, anti-angiogenic TKIs plus chemotherapy demonstrated superior second-line or above therapeutic efficacy for advanced or metastatic gastric cancer with well tolerated toxicity. However, TKIs + ICIs failed to demonstrate a clinical advantage over chemotherapy.

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura: Real-World Multicenter Data on Re-Administration and Plasma Exchange Free Treatment

Background Caplacizumab is the first targeted therapy, approved for acquired thrombotic thrombocytopenic purpura (aTTP). Our multicenter real-world study was designed to assess real-world outcomes of caplacizumab compared to historic controls, emphasizing on re-administration of caplacizumab and plasma-exchange free treatment. Methods: We recorded clinico-biological data from adult patients treated for aTTP over the last decade (2011-2021) according to current treatment guidelines. Diagnosis was confirmed with ADAMTS13 activity. Results are presented as median, range. Results: We have studied 66 patients (age 47 years, 19-75): 19 in the caplacizumab and 47 in the historic control group (Figure A). Patients that received caplacizumab had lower hemoglobin levels at diagnosis (p=0.029), higher rate of underlying comorbidities (p=0.005), but lower rate of neurological involvement (p=0.001). No other significant differences were observed in patient or disease characteristics between groups. Caplacizumab was given at a median on day 5 (1-32) from diagnosis (10 mg daily) for 30 (6-40) doses. In four patients, caplacizumab was administered after refractoriness to plasma exchange. In two patients, aTTP occurred early after COVID-19 infection. There were no major hemorrhagic events or other grade 3 complications. Median plasma exchange sessions were 12 (8-23) in caplacizumab group, versus 14 (6-32) in the control group. Early platelet normalization was achieved in all patients, following 5 (3-7) days from caplacizumab administration. ADAMTS13 activity normalized at the end of treatment in all caplacizumab-treated patients (25-52%). Two relapses have been observed within 13 and 18 months of the first caplacizumab administration, with low ADAMTS13 levels (<1%). In the first patient, caplacizumab was re-administered at regular dosing from day 1 of relapse, together with steroids but without plasma exchange. In the second patient, caplacizumab was started 10 days after initial relapse, because of poor response to plasma exchange and steroids. A rapid normalization of platelet count was observed in both patients within 10 and 4 days respectively, from the start of caplacizumab. Control patients presented 1 (0-14) relapse. After a median of 19.0 (2.6-320) months from aTTP diagnosis, there were 4 deaths (only from the control group, p-0.262, Figure B). Conclusion: Our real-world multicenter study provides updated data showing that caplacizumab is safe and effective in aTTP, even in patients refractory to plasma exchange, after re-administration, and in patients, who have not received plasma exchange treatment. Further studies in large real-world populations with longer follow-up are needed to delineate the algorithm of aTTP treatment in the era of personalized medicine. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A novel signature to predict the neoadjuvant chemotherapy response of bladder carcinoma: Results from a territory multicenter real-world study.

Background: Although neoadjuvant chemotherapy (NAC) has become the standard treatment option for muscle invasive bladder carcinoma (MIBC), its application is still limited because of the lack of biomarkers for NAC prediction. Methods: We conducted a territory multicenter real-world study to summarize NAC practice in China and its associated clinicopathologic variables with NAC response. Then, we developed and validated a robust gene-based signature for accurate NAC prediction using weighted correlation network analysis (WGCNA), the least absolute shrinkage and selector operation (LASSO) algorithm, a multivariable binary logistic regression model, and immunohistochemistry (IHC). Results: In total, we collected 69 consecutive MIBC patients treated with NAC from four clinical centers. The application of NAC in the real world was relatively safe, with only two grade Ⅳ and seven grade Ⅲ AEs and no treatment-related deaths being reported. Among these patients, 16 patients gave up surgery after NAC, leaving 53 patients for further analysis. We divided them into pathological response and non-response groups and found that there were more patients with a higher grade and stage in the non-response group. Patients with a pathological response could benefit from a significant overall survival (OS) improvement. In addition, univariate and multivariate logistic analyses indicated that tumor grade and clinical T stage were both independent factors for predicting NAC response. Importantly, we developed and validated a five-gene-based risk score for extremely high predictive accuracy for NAC response. Conclusion: NAC was relatively safe and could significantly improve OS for MIBC patients in the real-world practice. Our five-gene-based risk score could guide personalized therapy and promote the application of NAC.

Safety and efficacy of compound methyl salicylate liniment for topical pain: A multicenter real-world study in China.

Compound methyl salicylate liniment (Ammeltz) is composed of various components, such as methyl salicylate, menthol, camphor, chlorpheniramine maleate, and thymol. It was approved for listing in China in 2011. The purpose of this phase Ⅳ clinical trial was to evaluate the safety and efficacy of Ammeltz in a real-life environment in China. Adverse events and adverse drug reactions were used to assess the safety of the monitored drugs. Visual analog scale (VAS) scores were evaluated to assess the severity of pain and the pain relief rate was used to evaluate the efficacy of the study drug. Of 3,600 subjects enrolled, 3,515 (97.64%) subjects completed the study and 85 (2.36%) terminated the study prematurely. A total of 277 adverse events occurred in 258 subjects (7.28%). The most common adverse events included upper respiratory infections (130 cases, 3.67%), local pruritus (17 cases, 0.48%), and diarrhea (12 cases, 0.34%). A total of 50 (1.41%) subjects experienced 58 adverse drug reactions. The most common adverse drug reactions included local pruritus (17 cases, 0.48%), a burning sensation at the application site (10 cases, 0.28%), and irritation at the application site (local) (7 cases, 0.2%). No adverse reactions were identified as new adverse drug reactions. The majority of adverse drug reactions were mild (48 cases, 1.36%), and no severe adverse drug reactions occurred. The subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.34 vs. 2.79; Day 7 ± 1 vs. Baseline; p < 0.0001). The pain relief rate was 47.11% ± 23.13%, and in 2,769 cases (78.31%) the drug was effective in pain relief. After excluding subjects who used drugs that could affect the efficacy of the study drug, the subgroups of subjects experienced significant pain relief after using Ammeltz (mean VAS scores: 5.31 vs 2.77; Day 7 ± 1 vs Baseline; p < 0.0001). The pain relief rate was 47.34% ± 23.00%, and 2,612 subjects (78.75%) experienced effective pain relief. In conclusion, Ammeltz is safe and effective in real-life use. It can significantly relieve soft tissue pain caused by shoulder and neck pain, back pain, or muscle pain. No new adverse drug reactions were found in our multicenter real-world study. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05489939?cond=Safety+and+efficacy+of+compound+methyl+salicylate+liniment+for+topical+pain%3A+A+multicenter+real-world+study+in+China&draw=2&rank=1, identifier NCT05489939.