Prospective Real-world Study Research Articles

Efficacy and safety of eribulin as a front-line treatment in patients with advanced breast cancer: The first large scale prospective real-world study in China.

e13127 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for third-line treatment of advanced breast cancer (ABC) in China in 2019. However, efficacy and safety data for eribulin in Chinese patients with ABC are lacking, regardless of the therapy line. This study evaluated the efficacy, safety, and treatment pattern of eribulin in first- to third-line settings in Chinese patients with ABC. Methods: Patients with histologically confirmed ABC who had received ≤2 lines of prior treatment for metastatic disease were enrolled. Patients with HR+/HER2- ABC received eribulin monotherapy; those with HER2+ ABC received eribulin plus anti-HER2 targeted therapy, and those with metastatic triple-negative breast cancer (mTNBC) received eribulin plus immunotherapy/chemotherapy. The primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: In total, 160 patients were enrolled from 1 January 2021 to 31 December 2022 and 142 received study treatment. Eribulin was administered as first-line therapy in 41 (28.9%) patients, second-line therapy in 50 (35.2%), and third-line therapy in 51 (35.9%). The DCR was 71.6%; 55 patients (45.8%) had stable disease and 31 patients (25.8%) had complete or partial remission. The 6-month PFS rates (95% confidence interval [CI]) were: overall, 68.4% (58.0%, 76.8%); first-line eribulin, 75.4% (54.9%, 87.6%); HR+/HER2- ABC, 67.4% (53.8%, 77.7%); HER2+ ABC, 70.1% (38.5%, 87.6%); mTNBC, 69.5% (46.3%, 84.2%). PFS data were immature; the median (range) PFS was not reached with first-line eribulin and was 11.8 (3.3, 11.8) months with second-line eribulin. Subgroup analyses are shown in the Table; the 6-month PFS rate was 64.3% versus 74.0% in patients with versus without visceral metastases (p=0.25364). Common treatment-related adverse events (AEs) were hematological toxicities including leukopenia (9.5%), neutropenia (5.3%), and hypochromia (7.3%). There were no grade ≥3 AEs or AE-related treatment discontinuations. Conclusions: There was no significant difference in the efficacy analysis between the subgroup with visceral metastases and the subgroup without visceral metastases. Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity in patients with ABC. Clinical trial information: NCT04683445 . [Table: see text]

Tolerability and effectiveness of fulvestrant as first-line endocrine therapy in unselected patients with advanced breast cancer (ABC): Results of a multicenter, single arm, non-interventional study.

e13061 Background: Fulvestrant, a selective estrogen receptor (ER) down-regulator, is a standard of care for first-line treatment in hormone receptor-positive (HR+) advanced breast cancer. This study is to assess the safety profile and effectiveness of fulvestrant 500mg as the first-line endocrine therapy of post-menopausal women with HR+ locally advanced or metastatic breast cancer. Methods: The study is an open-label, multicentre, prospective, observational study in China. Chinese patients receiving fulvestrant 500mg as the first endocrine agent after relapse according to investigator’s clinical practice were enrolled. Primary variable is the frequency and severity of adverse events (AEs). Secondary variables were objective response rate (ORR), clinical benefit rate (CBR), progress free survival (PFS) and overall survival (OS). Predictive effects of endocrine resistance, chemotherapy for advanced disease and adjuvant endocrine therapy on the effectiveness were prespecified as exploratory variables. Results: From November 2017 to December 2020, 461 patients were enrolled by 29 Chinese centers. Median age was 56 years and the ECOG score was: 0, 165 (35.8%); 1, 281 (60.9%); 2, 12 (2.6%); and 3, 3 (0.7%). 20 (4.3%) patients had the Kaplan-Feinstein index ≥2. Majority (77.0%) of the patients were ER+ and PgR+, and 190 (41.2%) had visceral metastasis. In total, 91 (19.7%) patients were primary endocrine resistant, 202 (43.8%) were secondary endocrine resistant and 123 (26.7%) were endocrine-therapy naïve. 147 (31.9%) patients received previous chemotherapy for advanced disease, while 101 (21.9%) patients had anti-estrogen drugs as adjuvant therapy. 54 (11.7%) patients had concurrent CDK4/6 inhibitors. After a median follow-up of 26.8 months (IQR 18.7-38.2), median PFS was 13.0 months (95% CI 9.8-16.4) and median OS was 41.2 months (95% CI 37.3-NE). ORR was 11.3% (95% CI 8.2-15.1) and CBR was 60.6% (95%CI 55.2-65.8). Patients with endocrine-therapy naïve tumor, no previous chemotherapy for advanced disease and adjuvant anti-estrogen treatment had a longer PFS of first-line fulvestrant 500mg. 67 (14.5%) patients had at least one AE, with 1 (0.2%) patient withdrawing because of AEs. Drug-related serious AEs (SAEs) were rare, occurring in 2 (0.4%) patients. No patient died as a result of a drug-related AE. Neutropenia, increased ALT/AST, and anemia were the most commonly reported AEs in this study. Conclusions: This is the first prospective real-world study confirming that fulvestrant 500mg is a well-tolerated treatment option in unselected ABC in China. In the real clinical practice, fulvestrant 500mg can achieve the consistent anti-tumor activity as in clinical trials. Patients with endocrine-therapy naïve status and no prior chemotherapy tend to have a longer control time. Clinical trial information: NCT02909361 .

Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study

BackgroundPolymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens.MethodsPatients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy.ResultsA total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial.ConclusionsFor CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.

Motor Function and Quality of Life Improvement following Asleep versus Awake Deep Brain Stimulation (DBS) Procedures (P4-11.009)

<h3>Objective:</h3> To compare real-world outcomes in patients with Parkinson’s disease (PD) whose Deep Brain Stimulation (DBS) leads were implanted using asleep procedures versus those patients that underwent the procedure using awake conditions. <h3>Background:</h3> DBS procedures are typically conducted with patients being awake to allow for intraoperative clinical testing and/or micro-electrode recording to confirm lead location. However, asleep DBS procedures (i.e., under general anesthesia) are becoming increasingly popular due, at least in part, to technological improvements in imaging allowing alternative lead placement confirmation and shorter procedure duration (Brodsky 2017, Chen 2018, Vinke 2022). <h3>Design/Methods:</h3> A sub-analysis of patients receiving their DBS lead implant under asleep versus awake conditions was conducted in an ongoing, large, multicenter, prospective real-world outcomes study (Vercise, Boston Scientific). Motor function (MDS-UDPRS III), quality of life (PDQ-39) and related outcomes (GIC) were collected at baseline and up to 3-years. Safety events were also collected. <h3>Results:</h3> To date, 157 patients (mean age 61.2±8.3 years; 69% male) were asleep and 433 (mean age 60.1±8.5 years; 66% male) were awake during lead placement. Patients in both groups presented with similar baseline age, duration of disease and disease state. Improvement in quality-of-life was noted in both groups with a 5.3-point improvement (n = 104) in asleep group and a 4.5-point improvement (n = 319) in awake group at 1-year. Similarly, an 18.8- and 20.9-point improvement in motor function was noted in the asleep and awake groups, respectively. <h3>Conclusions:</h3> Outcomes from this large dataset of real-world outcomes examining the outcomes following asleep versus awake DBS demonstrate an alignment with results from previous studies (Holewijn 2021; LaHue 2017). Patient outcomes show little to no difference between awake versus asleep groups. Sleep DBS procedures may offer potential for shortening the total time taken for DBS procedures and offer a viable alternative for patients. <b>Disclosure:</b> Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific . Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbott . Jan Vesper has received research support from German Research Council. Dr. Deuschl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Cavion Functional Neuromodulation. The institution of Dr. Deuschl has received research support from Medtronic. Dr. Deuschl has received publishing royalties from a publication relating to health care. Lilly Chen has received personal compensation for serving as an employee of Boston Scientific . Roshini Jain has received personal compensation for serving as an employee of Boston Scientific. Roshini Jain has received stock or an ownership interest from Boston Scientific.

Evaluation of Angiotensin Receptor and Neprlysin Inhibition (ARNI) in Patients of Heart Failure with Reduced Ejection Fraction (HFrEF) - a real-world study

Objectives: This is a real world prospective study to evaluate the effects of Neprlysin Inhibition (ARNI) using sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methodology: This was an outpatient study on patients of HFrEF (EF&lt;40%) and stable blood pressure after obtaining informed consent. Consecutive patients were enrolled and followed at 6 and 12 weeks. Detailed clinical and echocardiographic examinations were performed on all visits. Biochemistry evaluating ProBNP, renal profile, HbA1C and electrolytes were performed in 24 patients at baseline and follow-up. Results: We enrolled 80 patients, but 63 patients could be followed. Mean age was 53.54±13.32 years and 55% were males. After 12 weeks treatment improvement in NYHA functional class was seen in 66% and improvement by more than one grade in 31% (p&lt;0.01). Pro-BNP reduced from 3552.71±1804.74 at the baseline to 723±930 on the second FU visit (p&lt;0.002). Structural improvement was seen in 33% of patients. Left ventricular (LV) end-diastolic diameter (EDD) reduced by 3.49 mm and LV end systolic diameter (ESD) by 3.97 mm (p&lt;0.014). Fractional shortening (FS) increased by 2.07% and EF by 3.52 (p&lt;0.01). Patients tolerated the drug well, but most could not tolerate the higher recommended dosage. Renal status, electrolytes, and HbA1C did not alter significantly. Conclusion: Treatment with sacubitril/valsartan in addition to the guideline directed medical therapy (GDMT) resulted in marked reduction in ProBNP, significant improvement in functional class and enhancement of cardiac pumping activity with reduction in LVEDD and LVESD and improvement in FS and EF.

48P Characteristics and treatment patterns of patients with advanced or metastatic non-small cell lung cancer managed with first-line immuno-oncology strategies in Greece: Interim results of a real-world prospective study (IO-HORIZON)

48P Characteristics and treatment patterns of patients with advanced or metastatic non-small cell lung cancer managed with first-line immuno-oncology strategies in Greece: Interim results of a real-world prospective study (IO-HORIZON)

Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study

IntroductionLEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. MethodsThis is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. Results161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). ConclusionsUnlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study.

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC). Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records. Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies. Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

Effectiveness of anti-interleukin-23 therapy in psoriatic arthritis: A pilot prospective real-world study.

This study aimed to show the effectiveness of interleukin (IL)-23 inhibitors in psoriatic arthritis (PsA) at weeks 12 and 24 in a real-world setting. Forty-three patients with active PsA were enrolled in this study. These patients were treated with either guselkumab (n= 20) or risankizumab (n= 23). Treatment responses at the 12th and 24th weeks were evaluated with the parameters of the number of joints with active arthritis, Psoriasis Area Severity Index (PASI) response rate, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, Disease Activity Index for Psoriatic Arthritis (DAPSA) score, and C-reactive protein (CRP) value. The study's primary endpoint was BASDAI ≤ 4 and DAPSA ≤ 14 at week 24, and the secondary endpoint was the absence of joints with clinically active arthritis signs at week 24. IL-23 inhibition significantly improved all treatment response parameters at the 12th and 24th weeks (P< 0.001). While 90% of patients reached the primary endpoint with anti-IL23 therapy, 74% achieved the secondary endpoint. Both biologic-naïve and biologic-experienced patients responded significantly to anti-IL-23 therapy. Also, no adverse events related to anti-IL-23 agents were observed. The response parameters indicating the severity of PsA (the number of joints with active arthritis, BASDAI score, DAPSA score, and CRP value) and a parameter indicating the severity of skin involvement, that is, PASI score, significantly improved with anti-IL-23 therapy at weeks 12 and 24. Moreover, significant improvement was achieved at week 24 compared to week 12 in all response parameters.

Factor Analysis in Distinguishing Coronavirus Disease 2019 From Other Influenza-like Illness Using a Validated Patient-Reported Outcome Instrument FLU-PRO Plus: A Prospective Real-world Cohort Study.

InFLUenza Patient-reported Outcome (FLU-PRO Plus) is a 34-item patient-reported outcome instrument designed to capture the intensity and frequency of viral respiratory symptoms. This study evaluates whether FLU-PRO Plus responses could discriminate between symptoms of coronavirus disease 2019 (COVID-19) and influenza-like illness (ILI) with no COVID diagnosis, as well as forecast disease progression. FLU-PRO Plus was administered daily for 14 days. Exploratory factor analysis was used to reduce the FLU-PRO Plus responses on the first day to 3 factors interpreted as "symptom clusters." The 3 clusters were used to predict COVID-19 versus ILI diagnosis in logistic regression. Correlation between the clusters and quality of life (QoL) measures was used to assess concurrent validity. The timing of self-reported return to usual health in the 14-day period was estimated as a function of the clusters within COVID-19 and ILI groups. Three hundred fourteen patients completed day 1 FLU-PRO Plus, of which 65% had a COVID-19 diagnosis. Exploratory factor analysis identified 3 symptom clusters: (1)general Body, (2) tracheal/bronchial, and (3) nasopharyngeal. Higher nasopharyngeal scores were associated with higher odds of COVID-19 compared with ILI diagnosis [adjusted odds ratio = 1.61 (1.21, 2.12)]. Higher tracheal/bronchial scores were associated with lower odds of COVID-19 [0.58 (0.44, 0.77)]. The 3 symptom clusters were correlated with multiple QoL measures ( r = 0.14-0.56). Higher scores on the general body and tracheal/bronchial symptom clusters were associated with prolonged time to return to usual health [adjusted hazard ratios: 0.76 (0.64, 0.91), 0.80 (0.67, 0.96)]. Three symptom clusters identified from FLU-PRO Plus responses successfully discriminated patients with COVID-19 from non-COVID ILI and were associated with QoL and predicted symptom duration.

Abstract P1-12-11: Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer

Abstract Objective: Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, showed promising efficacy and manageable safety profiles in the treatment of HER-2 positive breast cancer. Diarrhea is the most common adverse event associated with pyrotinib. This study aimed to evaluate the incidence and management of diarrhea secondary to pyrotinib in Chinese patients with HER-2 positive breast cancer. Methods: In this prospective real-world study, consecutive patients aged over 18 with HER-2 positive breast cancer and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 who planned to receive pyrotinib-based regimens for at least 21 days were included. Pyrotinib-treated patients and those with preexisting gastrointestinal conditions were excluded. There were no planned management strategy or primary prophylaxis for diarrhea, while loperamide, montmorillonite powder or Golden Bifid (a live combined Bifidobacterium, Lactobacillus and Streptococcus Thermophilus tablet) were recommended. Treatment was given in accordance with routine clinical practice by investigators. For patients developed grade 3 or higher diarrhea, pyrotinib was suspended until the diarrhea improving to grade 1 or less, and secondary prophylaxis (such as loperamide, loperamide plus montmorillonite powder, or loperamide plus Golden Bifid) was administrated before pyrotinib resumption. The baseline characteristics of patients and details of diarrhea (onset time, duration, severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03, treatment and prognosis) were collected. Results: Between August, 2020 and April, 2022, a total of 107 eligible patients were included, with a median age of 54 (range: 25-81) years old. Most patients (93.5%) had an ECOG PS of 0-1, and 51 patients (47.7%) were hormone receptor positive. A total of 46 patients (43.0%) received pyrotinib in the early stage and 61 (57.0%) in the advanced stage. Sixty-nine cases (64.5%) used pyrotinib-containing combination therapy (including 40 combined with capecitabine, 13 combined with trastuzumab, and 16 combined with other regimens), and 38 (35.5%) received pyrotinib alone. Ninety-eight cases (91.6%) reported diarrhea of any grade. Grade 1, 2 and 3 diarrhea occurred in 78 (72.9%), 9 (8.4%) and 11 (10.3%) patients, respectively. The median time to first onset of diarrhea of any grade was 2.5 (1-12) days, and the duration of first onset was 4 (1-24) days. The cumulative duration of diarrhea was 10 (1-60) days. Sixty-four, two, thirty, two patients used loperamide alone, montmorillonite powder alone, loperamide plus montmorillonite powder and loperamide plus Golden Bifid for the treatment of diarrhea, respectively. Eleven (10.3%) and seven (6.5%) patients experienced pyrotinib dose reduction and pyrotinib discontinuation. For 11 patients suffered grade 3 diarrhea, the median time to first onset of grade 3 diarrhea was 9 (4-14) days. Two, four and five patients administrated loperamide, loperamide plus Golden Bifid and loperamide plus montmorillonite powder as their secondary prophylaxis. Ten of eleven had grade 1 or 2 diarrhea after secondary prophylaxis, while one patient still suffered grade 3 diarrhea. All of them (11/11) held the pyrotinib dose. The incidence rate of constipation of all patients was 3.7%, which did not increase after treatment or secondary prophylaxis for diarrhea. Conclusion: In this study, the majority of patients developed pyrotinib associated diarrhea, and most of them were grade 1. About 10% patients reported grade 3 diarrhea, which can be managed by loperamide-based treatment and secondary prophylaxis. Table 1. Baseline characteristics of patients ECOG PS: Eastern Cooperative Oncology Group performance status; HER-2: human epidermal growth factor receptor 2. Table 2. Summary of patients developed diarrhea Table 3. Summary of patients developed grade 3 diarrhea Citation Format: Hong Liu, Li Ma, Xu Wang, Xinzhong Chang, Qi Yu, Qingfeng Huang, Chunfang Hao, Jun Liu, Jing Zhao, Shufen Li, Zhongsheng Tong, Yehui Shi, Ning Lu, Weipeng Zhao, Tong Wang, Xuchen Cao, Chen Wang, Juntian Liu, Ying Zhao, Lina Zhang, Baoliang Guo, Xin Wang, Xu Di, Chunhui Gao, Zongzhan Liu, Shuo Sun, Linwei Li. Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer [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 P1-12-11.

Predictors of response to galcanezumab in patients with chronic migraine: a real-world prospective observational study.

Despite high efficacy and tolerability, not all patients with chronic migraine benefit from anti-CGRP monoclonal antibodies. We aimed to identify the clinical predictors of the response to galcanezumab treatment in patients with chronic migraine from real-world data. We prospectively recruited patients with CM who underwent galcanezumab injections between December 2019 and February 2022. Treatment response was determined after three months of follow-up and was defined as ≥ 50% reduction in monthly headache days. The migraine characteristics, comorbidities, and other treatment responses were compared between the responder and non-responder groups. Of 238 patients with CM, 153 (64.3%) showed treatment response. The responder group was younger, had lower frequency of baseline headache days, and had more accompanying symptoms such as nausea, vomiting, and photophobia. Better triptan response and less depression were also observed in the responder group. Multivariable regression analysis revealed that the everyday headache (OR = 0.351, 95% CI = 0.133-0.874, p = 0.017), depression (OR = 0.439, 95% CI = 0.216-0.896, p = 0.024) and absence of accompanying symptoms (OR = 0.314, 95% CI = 0.118-0.834, p = 0.020) were significantly associated with response to galcanezumab treatment. Our real-world data showed the efficacy of galcanezumab in patients with CM, regardless of medication overuse. Everyday headache, presence of depression, and absence of accompanying symptoms of migraine were significant predictors of a poor response.

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.

Prognostic stratification by the Meet-URO score in a real-world elderly population of patients (pts) with metastatic renal cell carcinoma (mRCC) receiving cabozantinib: A subanalysis of the prospective ZEBRA study (Meet-URO 9).

637 Background: The combination of neutrophil to lymphocyte (NLR), bone metastases and IMDC score in the novel prognostic Meet-URO score has shown a higher prognostic performance than the IMDC score alone in mRCC pts receiving ≥2nd line nivolumab or cabozantinib in two retrospective analyses and 1st line nivolumab-ipilimumab in a real-world prospective study [http://bit.ly/Meet-URO15_score]. Further validation is needed since this score represents an easy prognostic tool for clinical practice with no additional costs. Methods: A real-world analysis of elderly (≥70 yo) mRCC pts treated with any line cabozantinib was conducted in the multicenter observational prospective Zebra study. Baseline Meet-URO score was assessed. The primary endpoint was overall survival (OS) and the Harrell’s c-index was calculated to compare accuracy of survival prediction of the Meet-URO and IMDC scores. Results: 104 mRCC pts received cabozantinib as 1st (38%), 2nd (20%), 3rd (33%) and 4th (8%) line, with a median follow-up of 11.2 months (mo) and a median overall survival (mOS) of 18.4 mo. According to the IMDC score, favorable- (15%), intermediate- (65%) and poor-risk (19%) pts had a mOS not reached (NR), 15.6 and of 5.7 mo, respectively (p = 0.011). Reclassifying the population according to the Meet-URO score, we observed that group 1 (10%) and group 2 (25%) had both mOS NR, whereas group 3 (33%), group 4 (25%) and group 5 (8%) had a mOS of 13.6, 12.5 and 3.7 mo, respectively (p = 0.001). Moreover, the Meet-URO score maintained its discrimination ability also merging group 1-2 vs 3-4 vs 5 (p &lt; 0.001). NLR &lt; 3.2 was the heaviest component of the score (p &lt; 0.001, mOS 24.8 vs 11.5 mo). The Meet-URO score (using both original with 5 groups and modified with 3 groups) has shown a higher prognostic power than the IMDC score alone (c-index of 0.686 and 0.676 vs 0.622). Conclusions: This analysis confirmed the higher accuracy in survival stratification of the Meet-URO score compared with the IMDC score alone also in a specific population like elderly mRCC pts treated with cabozantinib. NLR was confirmed as a strong prognostic factor with cabozantinib. Further applications of the Meet-URO score in mRCC pts treated with first-line immune-combinations are planned and highly awaited. Clinical trial information: 2018/116/PU .

Artificial Intelligence Based Analysis of Corneal Confocal Microscopy Images for Diagnosing Peripheral Neuropathy: A Binary Classification Model.

Diabetic peripheral neuropathy (DPN) is the leading cause of neuropathy worldwide resulting in excess morbidity and mortality. We aimed to develop an artificial intelligence deep learning algorithm to classify the presence or absence of peripheral neuropathy (PN) in participants with diabetes or pre-diabetes using corneal confocal microscopy (CCM) images of the sub-basal nerve plexus. A modified ResNet-50 model was trained to perform the binary classification of PN (PN+) versus no PN (PN-) based on the Toronto consensus criteria. A dataset of 279 participants (149 PN-, 130 PN+) was used to train (n = 200), validate (n = 18), and test (n = 61) the algorithm, utilizing one image per participant. The dataset consisted of participants with type 1 diabetes (n = 88), type 2 diabetes (n = 141), and pre-diabetes (n = 50). The algorithm was evaluated using diagnostic performance metrics and attribution-based methods (gradient-weighted class activation mapping (Grad-CAM) and Guided Grad-CAM). In detecting PN+, the AI-based DLA achieved a sensitivity of 0.91 (95%CI: 0.79-1.0), a specificity of 0.93 (95%CI: 0.83-1.0), and an area under the curve (AUC) of 0.95 (95%CI: 0.83-0.99). Our deep learning algorithm demonstrates excellent results for the diagnosis of PN using CCM. A large-scale prospective real-world study is required to validate its diagnostic efficacy prior to implementation in screening and diagnostic programmes.

Chidamide as maintenance after chemotherapy or hematopoietic stem cell transplantation in 27 children with T-cell lymphoblastic leukemia: A real-world prospective study.

The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi. This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months. In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease. The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children. https://www.chictr.org.cn/, identifier ChiCTR2000030357.

Efficacy and safety of anlotinib with PD-1 inhibitors in the treatment of advanced hepatocellular carcinoma: A real-world study.

583 Background: The IMbrave 150 study opened the door of immuno-oncology (IO) combined with targeted therapy in patients (pts) with hepatocellular carcinoma (HCC). At present, some other combination of IO and tyrosine kinase inhibitors (TKIs) had been proved as efficient regimens in China and there are many ongoing studies on this approach with preliminarily considerable efficacy. Furthermore, the efficacy of this combination still needs to be explored in real-world patients. The aim of this study is to explore the efficacy and safety of anlotinib plus PD-1 inhibitors in the treatment of HCC in real-world. Methods: This is a multi-center, prospective real-world study in pts (N=200) diagnosed as advanced HCC, who evaluated by physician would get benefits from anlotinib alone or in combination with PD-1 inhibitors. The enrolled patients received treatment according to physicians. Clinical efficacy was summarized, and adverse events were documented. Tumor response was assessed by investigators according to RECIST version 1.1. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Results: As of data cutoff date of Aug, 2022, a total of 119 patients were enrolled with a median age of 55 years (range 29-83). Among them 78% ECOG PS 0-1, 21% ECOG PS 2 and 1% ECOG PS 4. 75 pts received anlotinib plus PD-1 inhibitors as first-line treatment, 17 pts as second-line treatment and 7 pts as third-line and above. 76 patients were eligible for response evaluation. The ORR as best response was 11.8% (95%CI: 5.6%, 21.3%). The DCR was 73.7% (95%CI: 62.3%, 83.1%). The preliminarily results indicated that the median OS was 12.5 months (95%CI: 9.7, 15.4), the median PFS was 8.1 months (95%CI: 5.9, 10.3). Any grade treatment-related adverse events (TRAEs) observed in 50% of pts. The most common TRAEs were hypoalbuminemia (18.6%), hypertension (11.4%), decreased white blood cell count (11.4%) and decreased platelet count (10%). Conclusions: Present study indicated that the combination of anlotinib and PD-1 inhibitors exhibited potential efficacy and manageable adverse events in the treatment of advanced HCC in the real world. The conclusion should be validated in more patients included subsequently. Clinical trial information: NCT04954521 .

P573 Change in fatigue in patients with Ulcerative Colitis or Crohn’s disease initiating vedolizumab or other biologic therapy: Data from Belgian registry patients

Abstract Background Fatigue in patients (pts) with ulcerative colitis (UC) and Crohn’s disease (CD) is associated with decreased quality of life. This analysis aimed to describe fatigue evolution and identify factors associated with time to fatigue disappearance or fatigue persistence at 1 year among pts initiating vedolizumab (VDZ) or other biologic treatment (tx). Methods Post-hoc analysis of fatigue registry data of Belgian pts being followed in a prospective real-world safety study (PASS; NCT02674308). Pts ≥18 years with UC or CD initiating VDZ or other biologics with no prior VDZ exposure were included. Pts completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and physicians collected disease characteristics at baseline and 6-month intervals (4.5-year follow-up). Fatigue persistence was defined by 2 consecutive FACIT-F scores of &amp;lt;40, and fatigue disappearance (in pts with baseline fatigue) by a FACIT-F score of &amp;gt;40. Factors associated with time to fatigue disappearance and fatigue persistence at 1 year were assessed using multivariate regression. Results This analysis included 465 pts with UC (n=174) or CD (n=291) who initiated VDZ (n=259) or other biologic tx (n=206) at registry enrolment (Table 1 for baseline characteristics). Change in FACIT-F scores among all pts (Figure 1) showed an improvement in fatigue in the first 6-months following tx initiation before stabilising for the remainder of the study. The Kaplan-Meier estimate for time to fatigue disappearance (Figure 2) indicated fatigue disappearance occurred in 2.1%, 6.2% and 14.2% of pts with baseline fatigue at 6, 12 and 24-months respectively. In pts with baseline fatigue, lower likelihood of fatigue persistence was associated with achieving clinical remission (OR 0.31 [0.16, 0.60]). Probability of fatigue disappearance per unit of time was estimated to be higher in pts with UC vs CD (HR 1.53 [1.07, 2.21]) and in pts achieving vs not achieving clinical remission (HR 2.02 [1.18, 3.48]) and lower in pts with vs without extra-intestinal manifestations at baseline (HR 0.62 [0.39, 0.99]). No associations were observed between fatigue persistence/disappearance and tx group, demographics, disease duration, tx history, use of other medication, history of or active fistula, IBD surgery or clinical response. Conclusion These real-world findings suggest fatigue in pts initiating VDZ or other biologic therapy for UC or CD improves in the first 6 months of treatment before stabilising over time. Clinical remission was associated with a lower likelihood of fatigue persistence and shorter time to fatigue disappearance.

P503 The risk of mild, moderate and severe infections in IBD patients: results from a prospective, multicentre, observational cohort study – PRIQ

Abstract Background Immunomodulators and biologicals are essential in current IBD management, but are associated with increased risk of infections. Considering the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. To date, post-marketing surveillance studies mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. These infections take longer to clear in immunosuppressed patients and can substantially impact quality of life. We aimed to assess the incidence of all infections and identify risk factors for the development of infections in IBD patients. Methods We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients using the PRIQ implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Risk factors for infections were identified using multivariable logistic regression. Results In total, 629 IBD patients were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up, resulting in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively (Tables 1-2). Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections (Table 3). Compared to patients without treatment, patients on immunosuppressives more frequently experienced infections of any severity (mild: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p&amp;lt;0.001, moderate: IRR 1.42 [95%CI 1.20-1.69] p&amp;lt;0.001). On multivariable logistic regression, female sex (mild aOR 1.96; moderate aOR 1.71), smoking status (mild aOR 1.66; moderate aOR 1.86), higher BMI (moderate aOR 1.05), and more comorbidities (mild aOR 2.41; moderate aOR 1.82) were all significantly associated with the development of mild and moderate infections (Table 4). Conclusion In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

Prevalence of oral anticoagulant therapy in clinical practice in patients hospitalized with acute ischemic stroke

Aim. To evaluate the prevalence of oral anticoagulant therapy at the outpatient and inpatient stages in patients hospitalized with ischemic stroke.Material and methods. This open observational prospective real-world study included 114 patients with atrial fibrillation (AF) hospitalized with confirmed stroke.Results. Only 26,3% of patients with AF hospitalized with a confirmed diagnosis of ischemic stroke took anticoagulants (70% — direct oral anticoagulants (DOACs), 30% — warfarin). At the same time, among those taking warfarin, only one patient had normal international normalized ratio (INR) at the time of hospitalization (INR 2,6). In all other cases, the INR was &lt;2. Of the 105 patients discharged at the outpatient stage, 93 (88,6%) patients were prescribed anticoagulants, and in most cases — DOACs (89 (84,8%)). 4 (3,8%) patients insisted on continuing warfarin therapy. There were following reasons for not prescribing DOACs: 4 (33,3%) patients were diagnosed with acute peptic ulcer during hospitalization, 2 (16,7%) — hemorrhagic transformation of the ischemic focus.Conclusion. One of the common reasons for stroke in outpatients with AF is the refusal to take oral anticoagulants or insufficient INR control when taking warfarin.