Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.016
Sun Young Choi MD, PhD , A.M. Abd El-Aty , Beom Joon Kim MD, PhD
Purpose
Submental fat (SMF) accumulation can affect self-image and psychological well-being, leading to a demand for nonsurgical treatment. AYP-101, which contains soybean phosphatidylcholine (SPC), is under investigation for SMF reduction. This study aimed to compare 2 concentrations of AYP-101 to placebo injections to determine the optimal concentration and evaluate safety and efficacy in reducing moderate to severe SMF in an Asian population.
Methods
This single-center, randomized, double-blind, placebo-controlled phase II trial enrolled 96 participants with moderate to severe SMF. Participants were randomly assigned to receive either a placebo or AYP-101 at either a low concentration (25 mg/mL) or a high concentration (50 mg/mL), administered every 2 weeks for up to 6 sessions. The primary endpoint was the proportion of participants achieving at least a 1-grade improvement in both the Evaluator-Reported Submental Fat Rating Scale (ER-SMFRS) and the Subject-Reported Submental Fat Rating Scale (SR-SMFRS) at 4 and 12 weeks after the final injection.
Findings
At 4 weeks post-treatment, 69.70% of the low-concentration group and 48.39% of the high-concentration group exhibited improvement in the ER-SMFRS, compared to 22.58% in the placebo group. Significant differences were noted between the low-concentration and placebo groups (P = 0.0002), with similar results at 12 weeks.
Implications
AYP-101, administered biweekly at a concentration of 25 mg/mL, appears to be a safe and effective nonsurgical option for reducing SMF in Asians.
{"title":"Randomized, Double-Blind, Placebo-Controlled Phase II Trial of AYP-101 (Soybean Phosphatidylcholine) for Submental Fat Reduction in Asian Adults","authors":"Sun Young Choi MD, PhD , A.M. Abd El-Aty , Beom Joon Kim MD, PhD","doi":"10.1016/j.clinthera.2025.07.016","DOIUrl":"10.1016/j.clinthera.2025.07.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Submental fat (SMF) accumulation can affect self-image and psychological well-being, leading to a demand for nonsurgical treatment. AYP-101, which contains soybean phosphatidylcholine (SPC), is under investigation for SMF reduction. This study aimed to compare 2 concentrations of AYP-101 to placebo injections to determine the optimal concentration and evaluate safety and efficacy in reducing moderate to severe SMF in an Asian population.</div></div><div><h3>Methods</h3><div>This single-center, randomized, double-blind, placebo-controlled phase II trial enrolled 96 participants with moderate to severe SMF. Participants were randomly assigned to receive either a placebo or AYP-101 at either a low concentration (25 mg/mL) or a high concentration (50 mg/mL), administered every 2 weeks for up to 6 sessions. The primary endpoint was the proportion of participants achieving at least a 1-grade improvement in both the Evaluator-Reported Submental Fat Rating Scale (ER-SMFRS) and the Subject-Reported Submental Fat Rating Scale (SR-SMFRS) at 4 and 12 weeks after the final injection.</div></div><div><h3>Findings</h3><div>At 4 weeks post-treatment, 69.70% of the low-concentration group and 48.39% of the high-concentration group exhibited improvement in the ER-SMFRS, compared to 22.58% in the placebo group. Significant differences were noted between the low-concentration and placebo groups (<em>P</em> = 0.0002), with similar results at 12 weeks.</div></div><div><h3>Implications</h3><div>AYP-101, administered biweekly at a concentration of 25 mg/mL, appears to be a safe and effective nonsurgical option for reducing SMF in Asians.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 889-893"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.08.016
Paul Beninger MD, MBA
{"title":"Biomarkers: A Concept in Reach of Maturity","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.08.016","DOIUrl":"10.1016/j.clinthera.2025.08.016","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 827-829"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.08.001
Wei Wang MD , Zirui Dong MD , Qi Miao MD , Baoan Hong MD , Yuxuan Bo MD , Xuezhou Zhang MD , Xin Guan MD , Ning Zhang MD
Purpose
Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, either spontaneously or after therapy, leading to electrolyte imbalances that can result in acute kidney injury, arrhythmias, seizures, and multiorgan failure. Despite its clinical importance, the relationship between anticancer drugs and TLS, particularly newer targeted therapies, remains poorly understood.
Methods
We analyzed the US Food and Drug Administration (FDA) Adverse Events Reporting System database, a repository of adverse events associated with medical products, to identify TLS cases reported from the first quarter of 2004 to the third quarter of 2024. For signal detection, we used disproportionality analysis with 4 algorithms—reported odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. These algorithms assessed statistical correlations between anticancer drugs and TLS, based on a 2 × 2 contingency table framework.
Findings
From the first quarter of 2004 to the third quarter of 2024, a total of 7340 TLS cases were documented in the FDA Adverse Events Reporting System database. Clinical characteristics, including age, sex, and outcomes, were analyzed. Among all reported TLS cases, 53.0% were men, and the mean age across all individuals was 56.9 ± 21.5 years. The incidence of TLS peaked in 2022, with a 42% increase from 2016 to 2017. A total of 118 antineoplastic drugs were identified as highly associated with TLS, of which only 18 had FDA-labeled TLS-related adverse reactions. Chemotherapy drugs were the most frequently associated with TLS. Venetoclax emerged as the top drug associated with TLS, comprising 10.72% of all TLS reports.
Implications
Our findings highlight critical drug-induced TLS associations, particularly with emerging targeted therapies such as venetoclax. The study underscores the need for clinicians to monitor TLS closely in patients receiving certain anticancer treatments and to refine therapeutic strategies to mitigate TLS risk, ensuring safer cancer care outcomes. Further longitudinal studies are warranted to validate these findings and enhance pharmacovigilance efforts.
{"title":"Anticancer Drugs Associated With Tumor Lysis Syndrome: Insights From the US Food and Drug Administration Adverse Event Reporting System","authors":"Wei Wang MD , Zirui Dong MD , Qi Miao MD , Baoan Hong MD , Yuxuan Bo MD , Xuezhou Zhang MD , Xin Guan MD , Ning Zhang MD","doi":"10.1016/j.clinthera.2025.08.001","DOIUrl":"10.1016/j.clinthera.2025.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, either spontaneously or after therapy, leading to electrolyte imbalances that can result in acute kidney injury, arrhythmias, seizures, and multiorgan failure. Despite its clinical importance, the relationship between anticancer drugs and TLS, particularly newer targeted therapies, remains poorly understood.</div></div><div><h3>Methods</h3><div>We analyzed the US Food and Drug Administration (FDA) Adverse Events Reporting System database, a repository of adverse events associated with medical products, to identify TLS cases reported from the first quarter of 2004 to the third quarter of 2024. For signal detection, we used disproportionality analysis with 4 algorithms—reported odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. These algorithms assessed statistical correlations between anticancer drugs and TLS, based on a 2 × 2 contingency table framework.</div></div><div><h3>Findings</h3><div>From the first quarter of 2004 to the third quarter of 2024, a total of 7340 TLS cases were documented in the FDA Adverse Events Reporting System database. Clinical characteristics, including age, sex, and outcomes, were analyzed. Among all reported TLS cases, 53.0% were men, and the mean age across all individuals was 56.9 ± 21.5 years. The incidence of TLS peaked in 2022, with a 42% increase from 2016 to 2017. A total of 118 antineoplastic drugs were identified as highly associated with TLS, of which only 18 had FDA-labeled TLS-related adverse reactions. Chemotherapy drugs were the most frequently associated with TLS. Venetoclax emerged as the top drug associated with TLS, comprising 10.72% of all TLS reports.</div></div><div><h3>Implications</h3><div>Our findings highlight critical drug-induced TLS associations, particularly with emerging targeted therapies such as venetoclax. The study underscores the need for clinicians to monitor TLS closely in patients receiving certain anticancer treatments and to refine therapeutic strategies to mitigate TLS risk, ensuring safer cancer care outcomes. Further longitudinal studies are warranted to validate these findings and enhance pharmacovigilance efforts.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 844-850"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to evaluate the effects of azithromycin on lung function in children with cystic fibrosis (CF) through a systematic review and meta-analysis of randomized controlled trials (RCTs). The study primarily focuses on its impact on FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and the progression of lung function decline.
Methods
Electronic searches were conducted across PubMed,Cochrane Central, Embase, Web of Science, and China National Knowledge Infrastructure databases, including studies published up to November 1, 2024. Inclusion criteria required RCTs involving children with CF, azithromycin as the intervention, and placebo controls. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. Sensitivity analyses were conducted to ensure the robustness of results.
Findings
Eight RCTs were included, covering a total of 625 participants. Meta-analysis revealed that azithromycin significantly improved FEV1 compared to the control group, with a standardized mean difference (SMD) of 0.58 (95% CI: 0.03–1.14), though substantial heterogeneity was observed (I² = 82.8%). However, no statistically significant improvement in FVC was detected (SMD: 0.62, 95% CI: -0.04 to 1.29, I² = 85.4%). Additionally, azithromycin reduced the relative risk of lung function decline (RR: 0.79, 95% CI: 0.62–1.00), with moderate heterogeneity (I² = 45.5%). Sensitivity analyses confirmed the stability of these results.
Implications
Azithromycin shows potential in improving FEV1 and slowing lung function decline in children with cystic fibrosis, likely through its anti-inflammatory and immunomodulatory effects. Further large-scale studies are warranted to confirm its long-term efficacy, evaluate safety, and optimize treatment strategies, including potential combination therapies.
{"title":"The Impact of Azithromycin on Lung Function in Children And Adolescents with Cystic Fibrosis: A Systematic Review And Meta-Analysis","authors":"Kangping Wu MBBS , Suling Wu MBBS , Lina Wang MMed","doi":"10.1016/j.clinthera.2025.07.008","DOIUrl":"10.1016/j.clinthera.2025.07.008","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to evaluate the effects of azithromycin on lung function in children with cystic fibrosis (CF) through a systematic review and meta-analysis of randomized controlled trials (RCTs). The study primarily focuses on its impact on FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity), and the progression of lung function decline.</div></div><div><h3>Methods</h3><div>Electronic searches were conducted across PubMed,Cochrane Central, Embase, Web of Science, and China National Knowledge Infrastructure databases, including studies published up to November 1, 2024. Inclusion criteria required RCTs involving children with CF, azithromycin as the intervention, and placebo controls. Meta-analyses were performed using random-effects models, and heterogeneity was assessed using the I² statistic. Sensitivity analyses were conducted to ensure the robustness of results.</div></div><div><h3>Findings</h3><div>Eight RCTs were included, covering a total of 625 participants. Meta-analysis revealed that azithromycin significantly improved FEV1 compared to the control group, with a standardized mean difference (SMD) of 0.58 (95% CI: 0.03–1.14), though substantial heterogeneity was observed (I² = 82.8%). However, no statistically significant improvement in FVC was detected (SMD: 0.62, 95% CI: -0.04 to 1.29, I² = 85.4%). Additionally, azithromycin reduced the relative risk of lung function decline (RR: 0.79, 95% CI: 0.62–1.00), with moderate heterogeneity (I² = 45.5%). Sensitivity analyses confirmed the stability of these results.</div></div><div><h3>Implications</h3><div>Azithromycin shows potential in improving FEV1 and slowing lung function decline in children with cystic fibrosis, likely through its anti-inflammatory and immunomodulatory effects. Further large-scale studies are warranted to confirm its long-term efficacy, evaluate safety, and optimize treatment strategies, including potential combination therapies.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 918-924"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.005
Han Shan MS , Qiong Du MS , Mengmeng Wang MS
Purpose
Although the diagnostic potential of septin 9 methylation (mSEPT9) in colorectal cancer (CRC) has been well documented in numerous studies, its predictive role in determining therapeutic response to antitumor agents among patients with advanced CRC remains unexplored.
Methods
This real-world, large-scale retrospective study analyzed 1098 CRC cases selected from a comprehensive database of 1490 patients who underwent mSEPT9 testing. We first investigated the association between mSEPT9 status and clinicopathological characteristics in the overall CRC cohort. Subsequently, in a subset of 479 stage IV CRC patients receiving systemic antitumor therapy, we evaluated the predictive value of mSEPT9 status by assessing treatment outcomes, including objective response rate (ORR) and progression-free survival (PFS).
Findings
mSEPT9 positivity was significantly elevated in stage Ⅳ versus stage Ⅰ–Ⅲ patients and correlated with Eastern Cooperative Oncology Group (ECOG) score, but not with other clinicopathological features. mSEPT9-positive patients demonstrated significantly higher ORR to fluoropyrimidines, oxaliplatin, and bevacizumab compared with mSEPT9-negative patients, whereas no significant ORR differences were observed for irinotecan or cetuximab. Conversely, mSEPT9-positive patients showed shorter PFS with fluoropyrimidines, oxaliplatin, irinotecan, and cetuximab, but comparable PFS with bevacizumab between the 2 groups.
Implications
mSEPT9 status significantly correlated with CRC stage and ECOG score, influencing antitumor agents efficacy in advanced CRC. Although mSEPT9-positive patients showed higher ORR to certain agents, they exhibited shorter PFS, suggesting more aggressive tumor biology. Bevacizumab appeared to partially counteract the adverse prognostic impact of mSEPT9 positivity. This first demonstration of mSEPT9′s predictive value for advanced CRC treatment outcomes provides new insights for personalized therapy.
{"title":"Association of Plasma Septin9 Methylation Status With Therapeutic Response to Antitumor Agents in Colorectal Cancer Patients","authors":"Han Shan MS , Qiong Du MS , Mengmeng Wang MS","doi":"10.1016/j.clinthera.2025.07.005","DOIUrl":"10.1016/j.clinthera.2025.07.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Although the diagnostic potential of septin 9 methylation (mSEPT9) in colorectal cancer (CRC) has been well documented in numerous studies, its predictive role in determining therapeutic response to antitumor agents among patients with advanced CRC remains unexplored.</div></div><div><h3>Methods</h3><div>This real-world, large-scale retrospective study analyzed 1098 CRC cases selected from a comprehensive database of 1490 patients who underwent mSEPT9 testing. We first investigated the association between mSEPT9 status and clinicopathological characteristics in the overall CRC cohort. Subsequently, in a subset of 479 stage IV CRC patients receiving systemic antitumor therapy, we evaluated the predictive value of mSEPT9 status by assessing treatment outcomes, including objective response rate (ORR) and progression-free survival (PFS).</div></div><div><h3>Findings</h3><div>mSEPT9 positivity was significantly elevated in stage Ⅳ versus stage Ⅰ–Ⅲ patients and correlated with Eastern Cooperative Oncology Group (ECOG) score, but not with other clinicopathological features. mSEPT9-positive patients demonstrated significantly higher ORR to fluoropyrimidines, oxaliplatin, and bevacizumab compared with mSEPT9-negative patients, whereas no significant ORR differences were observed for irinotecan or cetuximab. Conversely, mSEPT9-positive patients showed shorter PFS with fluoropyrimidines, oxaliplatin, irinotecan, and cetuximab, but comparable PFS with bevacizumab between the 2 groups.</div></div><div><h3>Implications</h3><div>mSEPT9 status significantly correlated with CRC stage and ECOG score, influencing antitumor agents efficacy in advanced CRC. Although mSEPT9-positive patients showed higher ORR to certain agents, they exhibited shorter PFS, suggesting more aggressive tumor biology. Bevacizumab appeared to partially counteract the adverse prognostic impact of mSEPT9 positivity. This first demonstration of mSEPT9′s predictive value for advanced CRC treatment outcomes provides new insights for personalized therapy.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 830-836"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction notice to “Models for the prediction of mycophenolic acid area under the curve using a limited-sampling strategy and an enzyme multiplied immunoassay technique in chinese patients undergoing liver transplantation” [Clinical Therapeutics 30 (2008) 2387-2401]","authors":"Hao Chen MD, PhD , Zhidong Gu MD , Bing Chen MD, PhD , Huarong Mao MD , Weixia Zhang MD, PhD , Qishi Fan MD","doi":"10.1016/j.clinthera.2025.08.008","DOIUrl":"10.1016/j.clinthera.2025.08.008","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Page 956"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.003
H. Colinda Post , Charlotte H. C． Bomhof , Maartje Schermer , Carla E. M． Hollak , Hanneke W. M． van Laarhoven , Tim Schutte , Eline M． Bunnik
Purpose
Timelines for market authorization and reimbursement for anticancer medicines differ across European countries. Therefore, medical oncologists may face periods when promising anticancer medicines are not reimbursed, prompting ethical concerns about equitable access, particularly in publicly funded healthcare systems, such as the Netherlands. This study explores Dutch medical oncologists’ experiences and moral perspectives regarding access to EU-authorized nonreimbursed anticancer medicines and assesses practice variation.
Methods
A survey targeted 378 Dutch medical oncologists from all hospitals to explore their experiences, perspectives, and perceived responsibilities, as well as hospital policies regarding nonreimbursed EU-authorized anticancer medicines and their opinions on out-of-pocket payments and information provision.
Findings
Responses were provided by 132 medical oncologists (response rate of 34.9%), with 104 (78.8%) reporting that they sought access to nonreimbursed medicines in the past three years for one or more patients, primarily through manufacturer-funded “free-of-charge” programs (n = 77/104; 74,0%), clinical trials referral (n = 46/104; 44.2%) or clinical trials at their own hospital (n = 45/104; 43.3%), insurance leniency (n = 45/104; 43.3%), or the Dutch Drug Access Protocol (n = 42/104; 40.4%). While 48.5% felt responsible for seeking access to nonreimbursed medicines, 40.9% did not. Respondents mentioned different hospital policies on drug access. In the past three years, 69.5% (n = 91/131) of respondents had received patient inquiries about out-of-pocket (OOP) payment, but only 3.1% (n = 4/131) had actually prescribed OOP financed medicines. Fewer than half of the respondents (44.7%; n = 59/132) informed patients about nonreimbursed treatment options. Oncologists expressed strong concerns about financial toxicity, inequities in access, and threats to solidarity-based health care.
Implications
The majority of Dutch medical oncologists encounter EU-authorized, nonreimbursed anticancer medicines and report substantial variation in related practices and ethical views. In the absence of a national access framework, availability often depends on individual physicians, leading to potential inequities. National regulation is recommended to ensure consistent and equitable access for all patients.
{"title":"Access to EU-Authorized Nonreimbursed Anticancer Medicines: An Explorative Survey Among Dutch Medical Oncologists","authors":"H. Colinda Post , Charlotte H. C． Bomhof , Maartje Schermer , Carla E. M． Hollak , Hanneke W. M． van Laarhoven , Tim Schutte , Eline M． Bunnik","doi":"10.1016/j.clinthera.2025.07.003","DOIUrl":"10.1016/j.clinthera.2025.07.003","url":null,"abstract":"<div><h3>Purpose</h3><div>Timelines for market authorization and reimbursement for anticancer medicines differ across European countries. Therefore, medical oncologists may face periods when promising anticancer medicines are not reimbursed, prompting ethical concerns about equitable access, particularly in publicly funded healthcare systems, such as the Netherlands. This study explores Dutch medical oncologists’ experiences and moral perspectives regarding access to EU-authorized nonreimbursed anticancer medicines and assesses practice variation.</div></div><div><h3>Methods</h3><div>A survey targeted 378 Dutch medical oncologists from all hospitals to explore their experiences, perspectives, and perceived responsibilities, as well as hospital policies regarding nonreimbursed EU-authorized anticancer medicines and their opinions on out-of-pocket payments and information provision.</div></div><div><h3>Findings</h3><div>Responses were provided by 132 medical oncologists (response rate of 34.9%), with 104 (78.8%) reporting that they sought access to nonreimbursed medicines in the past three years for one or more patients, primarily through manufacturer-funded “free-of-charge” programs (<em>n</em> = 77/104; 74,0%), clinical trials referral (<em>n</em> = 46/104; 44.2%) or clinical trials at their own hospital (<em>n</em> = 45/104; 43.3%), insurance leniency (<em>n</em> = 45/104; 43.3%), or the Dutch Drug Access Protocol (<em>n</em> = 42/104; 40.4%). While 48.5% felt responsible for seeking access to nonreimbursed medicines, 40.9% did not. Respondents mentioned different hospital policies on drug access. In the past three years, 69.5% (<em>n</em> = 91/131) of respondents had received patient inquiries about out-of-pocket (OOP) payment, but only 3.1% (<em>n</em> = 4/131) had actually prescribed OOP financed medicines. Fewer than half of the respondents (44.7%; <em>n</em> = 59/132) informed patients about nonreimbursed treatment options. Oncologists expressed strong concerns about financial toxicity, inequities in access, and threats to solidarity-based health care.</div></div><div><h3>Implications</h3><div>The majority of Dutch medical oncologists encounter EU-authorized, nonreimbursed anticancer medicines and report substantial variation in related practices and ethical views. In the absence of a national access framework, availability often depends on individual physicians, leading to potential inequities. National regulation is recommended to ensure consistent and equitable access for all patients.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 894-903"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.012
Nadine de Godoy Torso MSc , Yasmim Gabriele Matos PharmB , Giovana Fernanda Santos Fidelis BPharm , Carolina Dagli-Hernandez PhD , Marília Berlofa Visacri PhD , Eder de Carvalho Pincinato PhD , Jefman Efendi Marzuki MD , Baharuddin Baharuddin MSc , Paulo Caleb J.L. Santos PhD , Patricia Moriel PhD
Purpose
Gynecological tumors, which correspond to the group of neoplasms that affect the female reproductive system, have high incidence and mortality rates. This systematic review aimed to summarize the most recent advances in identifying pharmacogenetic variants associated with the clinical outcomes of carboplatin-paclitaxel chemotherapy in these patients.
Methods
A comprehensive literature search was conducted across eight databases to identify studies published up to July 17, 2024. Two reviewers independently selected the studies and extracted the data; disagreements were resolved by two additional reviewers.
Findings
Out of the 2375 records that were found, only 20 met the eligibility criteria. The main findings were: (1) The three most extensively investigated genes were ATP binding cassette subfamily C member 1 (ABCB1), cytochrome P450 2C8 (CYP2C8), and glutathione S-transferase P1 (GSTP1); (2) three variants, rs1128503 (ABCB1), rs10509681 and rs11572080 (CYPC28), appear to have a significant association with important adverse drug reactions (in particular, neutropenia, thrombocytopenia, and peripheral sensory neuropathy). Others, as is the case with rs1045642 (ABCB1) and rs1695 (GSTP1), have inconsistent results, and the extent to which these results can be extrapolated is still limited; and (c) most of the included studies concerned Asian or European patients.
Implications
Therefore, future research should include more extensive analyses with more inclusive cohorts. As a limitation of the study, a meta-analysis was not possible due to the significant heterogeneity among the studies.
{"title":"Genetic Polymorphisms as Treatment Biomarkers for Gynecological Malignancies Treated With Carboplatin and Paclitaxel: A Systematic Review","authors":"Nadine de Godoy Torso MSc , Yasmim Gabriele Matos PharmB , Giovana Fernanda Santos Fidelis BPharm , Carolina Dagli-Hernandez PhD , Marília Berlofa Visacri PhD , Eder de Carvalho Pincinato PhD , Jefman Efendi Marzuki MD , Baharuddin Baharuddin MSc , Paulo Caleb J.L. Santos PhD , Patricia Moriel PhD","doi":"10.1016/j.clinthera.2025.07.012","DOIUrl":"10.1016/j.clinthera.2025.07.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Gynecological tumors, which correspond to the group of neoplasms that affect the female reproductive system, have high incidence and mortality rates. This systematic review aimed to summarize the most recent advances in identifying pharmacogenetic variants associated with the clinical outcomes of carboplatin-paclitaxel chemotherapy in these patients.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted across eight databases to identify studies published up to July 17, 2024. Two reviewers independently selected the studies and extracted the data; disagreements were resolved by two additional reviewers.</div></div><div><h3>Findings</h3><div>Out of the 2375 records that were found, only 20 met the eligibility criteria. The main findings were: (1) The three most extensively investigated genes were ATP binding cassette subfamily C member 1 (<em>ABCB1</em>), cytochrome P450 2C8 (<em>CYP2C8</em>), and glutathione S-transferase P1 (<em>GSTP1</em>); (2) three variants, rs1128503 (<em>ABCB1</em>), rs10509681 and rs11572080 (<em>CYPC28</em>), appear to have a significant association with important adverse drug reactions (in particular, neutropenia, thrombocytopenia, and peripheral sensory neuropathy). Others, as is the case with rs1045642 (<em>ABCB1</em>) and rs1695 (<em>GSTP1</em>), have inconsistent results, and the extent to which these results can be extrapolated is still limited; and (c) most of the included studies concerned Asian or European patients.</div></div><div><h3>Implications</h3><div>Therefore, future research should include more extensive analyses with more inclusive cohorts. As a limitation of the study, a meta-analysis was not possible due to the significant heterogeneity among the studies.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 904-917"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.014
Eunji Kim MS , Yu-Seon Jung PhD , Jongmin Lee PharmD, MS , Dal Ri Nam PharmD, MS , Seung-Hun You PhD , Ju Won Lee MS , Sook Ryun Park MD, PhD , Ji Seon Oh MD, PhD , Ye-Jee Kim PhD , Eun-Jung Jo MD, PhD , Nakyung Jeon PhD , Won-Jung Jung , Sun-Young Jung PhD
Purpose
This study was conducted to comprehensively understand the utilization patterns of immune checkpoint inhibitors (ICIs) in Korea, including their use in combination with traditional anticancer therapies.
Methods
We investigated the utilization of ICIs using claims data from Korea between 2017 and 2022. Patients with cancer were included in the study if they received at least one dose of ICIs, defined by drug codes in the claims data. We used descriptive statistics to identify patterns of ICIs use in combination with other anticancer therapies and ICIs use by year and cancer type.
Findings
During the study period, 41,208 patients received at least one dose of ICIs. Lung cancer (66.6%), urinary tract cancer (11.3%), and liver/biliary tract cancer (10.6%) were the most frequent cancer types. The prescription of ICIs particularly surged between 2020 and 2022 for liver/biliary tract cancer. Between 2017 and 2022, the use of ICIs increased from 1,155 to 15,034, with an increase every year. Since 2020, the use of ICIs in combination with other anticancer therapies and concurrent use of ICIs has increased sharply.
Implications
The number of patients utilizing ICIs in Korea has been steadily increasing. As regulatory approval of indications for ICIs has expanded, so has the range of indications for ICIs. In addition, the combination of ICIs with other anticancer therapies and the concurrent use of ICIs has increased in recent years, reflecting expanded treatment options for advanced cancers.
{"title":"Real-World Utilization Patterns of Immune Checkpoint Inhibitors Based on the National Health Insurance Service Data in Korea","authors":"Eunji Kim MS , Yu-Seon Jung PhD , Jongmin Lee PharmD, MS , Dal Ri Nam PharmD, MS , Seung-Hun You PhD , Ju Won Lee MS , Sook Ryun Park MD, PhD , Ji Seon Oh MD, PhD , Ye-Jee Kim PhD , Eun-Jung Jo MD, PhD , Nakyung Jeon PhD , Won-Jung Jung , Sun-Young Jung PhD","doi":"10.1016/j.clinthera.2025.07.014","DOIUrl":"10.1016/j.clinthera.2025.07.014","url":null,"abstract":"<div><h3>Purpose</h3><div>This study was conducted to comprehensively understand the utilization patterns of immune checkpoint inhibitors (ICIs) in Korea, including their use in combination with traditional anticancer therapies.</div></div><div><h3>Methods</h3><div>We investigated the utilization of ICIs using claims data from Korea between 2017 and 2022. Patients with cancer were included in the study if they received at least one dose of ICIs, defined by drug codes in the claims data. We used descriptive statistics to identify patterns of ICIs use in combination with other anticancer therapies and ICIs use by year and cancer type.</div></div><div><h3>Findings</h3><div>During the study period, 41,208 patients received at least one dose of ICIs. Lung cancer (66.6%), urinary tract cancer (11.3%), and liver/biliary tract cancer (10.6%) were the most frequent cancer types. The prescription of ICIs particularly surged between 2020 and 2022 for liver/biliary tract cancer. Between 2017 and 2022, the use of ICIs increased from 1,155 to 15,034, with an increase every year. Since 2020, the use of ICIs in combination with other anticancer therapies and concurrent use of ICIs has increased sharply.</div></div><div><h3>Implications</h3><div>The number of patients utilizing ICIs in Korea has been steadily increasing. As regulatory approval of indications for ICIs has expanded, so has the range of indications for ICIs. In addition, the combination of ICIs with other anticancer therapies and the concurrent use of ICIs has increased in recent years, reflecting expanded treatment options for advanced cancers.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 837-843"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.clinthera.2025.07.025
Na Zhou MSc, Jiao Xu BSc, Ling Liu PhD, Yichen Yang BSc, Xuejiao Fan MSc, Haiqin Ren MSc
Purpose
Large-scale data comparing the effects of combined letrozole (LE) and clomiphene citrate (CC) with gonadotropin (Gn) microstimulation protocols on pregnancy outcomes are lacking. This study aimed to compare the effects of CC + Gn and LE + Gn microstimulation protocols on fertility outcomes.
Methods
A retrospective cohort study was conducted to include infertile patients between January 1, 2018, and December 31, 2022. All patients underwent a microstimulation protocol and treatment was administered using either CC + Gn or LE + Gn. The main study outcomes included clinical pregnancy, miscarriage, and live birth rates.
Findings
Of the 1697 included patients, 875 were treated with CC + Gn, while the remaining 822 were treated with LE + Gn. We noted that CC + Gn was associated with a lower clinical pregnancy rate (odds ratio (OR): 0.324; 95% confidence interval (CI): 0.127–0.829; P = 0.019) and live birth rate (OR: 0.332; 95% CI: 0.112–0.988; P = 0.048) than LE + Gn; however, there was no significant difference between CC + Gn and LE + Gn regarding the abortion rate (OR: 0.523; 95% CI: 0.028–9.720; P = 0.664). Moreover, there were significant differences between the CC + Gn and LE + Gn groups in the number of embryos transferred (P < 0.001), number of frozen embryos (P < 0.001), and number of embryos at the frozen cleavage stage (P = 0.002).
Implications
LE + Gn microstimulation protocol was associated with better fertility outcomes than CC + Gn in terms of clinical pregnancy and live birth rates in patients with infertility.
{"title":"Comparison of Combined Letrozole and Clomiphene Citrate With Gonadotropin Microstimulation Protocols on Fertility Outcomes","authors":"Na Zhou MSc, Jiao Xu BSc, Ling Liu PhD, Yichen Yang BSc, Xuejiao Fan MSc, Haiqin Ren MSc","doi":"10.1016/j.clinthera.2025.07.025","DOIUrl":"10.1016/j.clinthera.2025.07.025","url":null,"abstract":"<div><h3>Purpose</h3><div>Large-scale data comparing the effects of combined letrozole (LE) and clomiphene citrate (CC) with gonadotropin (Gn) microstimulation protocols on pregnancy outcomes are lacking. This study aimed to compare the effects of CC + Gn and LE + Gn microstimulation protocols on fertility outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted to include infertile patients between January 1, 2018, and December 31, 2022. All patients underwent a microstimulation protocol and treatment was administered using either CC + Gn or LE + Gn. The main study outcomes included clinical pregnancy, miscarriage, and live birth rates.</div></div><div><h3>Findings</h3><div>Of the 1697 included patients, 875 were treated with CC + Gn, while the remaining 822 were treated with LE + Gn. We noted that CC + Gn was associated with a lower clinical pregnancy rate (odds ratio (OR): 0.324; 95% confidence interval (CI): 0.127–0.829; <em>P</em> = 0.019) and live birth rate (OR: 0.332; 95% CI: 0.112–0.988; <em>P</em> = 0.048) than LE + Gn; however, there was no significant difference between CC + Gn and LE + Gn regarding the abortion rate (OR: 0.523; 95% CI: 0.028–9.720; <em>P</em> = 0.664). Moreover, there were significant differences between the CC + Gn and LE + Gn groups in the number of embryos transferred (<em>P</em> < 0.001), number of frozen embryos (<em>P</em> < 0.001), and number of embryos at the frozen cleavage stage (<em>P</em> = 0.002).</div></div><div><h3>Implications</h3><div>LE + Gn microstimulation protocol was associated with better fertility outcomes than CC + Gn in terms of clinical pregnancy and live birth rates in patients with infertility.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 884-888"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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