Advances in Therapy最新文献

{"title":"Pembrolizumab in Patients of Chinese Descent with Microsatellite Instability-high/Mismatch Repair Deficient Advanced Solid Tumors: KEYNOTE-158 Final Analysis.","authors":"Xiaohua Wu, Yimin Mao, Nong Xu, Yuxian Bai, Dong Wang, Xiaojun Chen, Xianli Yin, Yanhong Deng, Jianwei Yang, Jieqing Zhang, Jie Tang, Yi Huang, Jiayi Li, Suxia Luo, Hong Zheng, Weidong Zhao, Miaomiao Xu, Nan Li, Yixiang Mao, Alexander Gozman, Jianming Xu","doi":"10.1007/s12325-025-03142-6","DOIUrl":"https://doi.org/10.1007/s12325-025-03142-6","url":null,"abstract":"<p><strong>Introduction: </strong>KEYNOTE-158 (NCT02628067) supported the US Food and Drug Administration approval of pembrolizumab for microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. Incidence of MSI-H/dMMR tumors in patients of Chinese descent is similar to that of Western populations. Cohort L of KEYNOTE-158 evaluated pembrolizumab in patients of Chinese descent with previously treated MSI-H/dMMR tumors. We previously reported an objective response rate (ORR) of 70% in 20 patients from cohort L which supported the approval in China of pembrolizumab in patients with MSI-H/dMMR solid tumors. Here we present results of the final analysis for 30 patients with median follow-up of 18 months.</p><p><strong>Methods: </strong>Eligible patients who had confirmed unresectable or metastatic MSI-H/dMMR tumors, and one or more prior lines of therapy, received 200 mg pembrolizumab Q3W (up to 35 cycles) until progression, toxicity, or withdrawal. Primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.</p><p><strong>Results: </strong>Thirty patients were enrolled; 7 (23%) were aged ≥ 65 years, and 20 (67%) were female. With median follow-up of 18 months, ORR was 66.7%. Median DOR was not reached (NR), with 12-month DOR rate of 85.9%. Median PFS was NR, with 18-month PFS rate of 63.0%. Median OS was NR, with 18-month OS rate of 78.8%. Treatment-related adverse events (AE) were reported in 22 (73%) patients. Grade 3-4 treatment-related AEs occurred in 7 (23%) patients. Immune-mediated AEs occurred in 11 (37%) patients of which 2 (7%) had grade 3 AEs. No grade ≥ 4 immune-mediated AEs occurred.</p><p><strong>Conclusion: </strong>Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in patients of Chinese descent with MSI-H/dMMR advanced solid tumors. These results are consistent with those reported for patients in the global population and further support the use of pembrolizumab in patients of Chinese descent with MSI-H/dMMR tumors. TRIAL REGISTRATION NUMBER: NCT02628067.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point of Care Nucleic Acid Testing for Influenza-Like Illness: A Cost-Consequence Analysis for High-Risk Patients in Primary Care in Germany.","authors":"Johannes Pöhlmann, Anika Joecker, Tanja Wittki, Tray Brown, Richard F Pollock, Jordan Chase","doi":"10.1007/s12325-025-03156-0","DOIUrl":"https://doi.org/10.1007/s12325-025-03156-0","url":null,"abstract":"<p><strong>Introduction: </strong>Influenza A/B virus, severe acute respiratory coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) cause similar symptoms, often referred to as influenza-like illness, but require different treatments which must be administered within a short timeframe after symptom onset. This necessitates rapid detection and accurate differentiation by primary care providers, ideally at point of care (POC). POC nucleic acid tests such as the multiplex, real-time polymerase chain reaction (PCR) Xpert^® Xpress CoV-2/Flu/RSV plus (Xpert Xpress) offer a faster, more accurate alternative compared to antigen testing, clinical judgement alone, or send-out PCR. This cost-consequence analysis evaluated Xpert Xpress versus conventional testing methods, from a German statutory health insurance (SHI) perspective.</p><p><strong>Methods: </strong>A 1-year decision tree was developed to compare Xpert Xpress with antigen testing, send-out PCR, and empiric diagnosis, for influenza A/B virus, SARS-CoV-2, and RSV. The model accounted for diagnostic accuracy and projected the share of patients receiving results within guideline-recommended treatment windows. Data on test accuracy, treatment effects, and costs were sourced from literature and German databases. The main outcome was total cost to the SHI for the 2023/24 respiratory illness season.</p><p><strong>Results: </strong>Xpert Xpress was associated with the highest number of net correct treatment courses (n = 443,600) versus empiric diagnosis (n = 239,250), antigen testing (n = 347,218), and send-out PCR (n = 280,527). Acquisition costs were highest for Xpert Xpress (EUR 38.4 million versus EUR 27.4 million for antigen testing and EUR 33.5 million for send-out PCR) but were offset by reduced hospitalization and intensive care costs. Overall, Xpert Xpress was associated with cost savings of EUR 1.97 million versus empiric diagnosis, EUR 10.1 million versus antigen testing, and EUR 20.8 million versus send-out PCR.</p><p><strong>Conclusions: </strong>Using Xpert Xpress at POC combined fast turnaround with high diagnostic accuracy, thereby increasing correct treatment courses while reducing total costs for influenza, COVID-19, and RSV, offering substantial savings to the German SHI.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials.","authors":"Yuki Otani, Brian G Feagan, Geert R D'Haens, Rodrigo Escobar, Nathan J Morris, Christopher D Payne, Michelle Ugolini Lopes, Xin Zhang","doi":"10.1007/s12325-025-03158-y","DOIUrl":"https://doi.org/10.1007/s12325-025-03158-y","url":null,"abstract":"<p><strong>Introduction: </strong>Mirikizumab, a p19-directed antibody against interleukin-23 (IL-23), is administered by subcutaneous (SC) injection. Injection site pain (ISP) associated with citrate buffers may negatively affect patient adherence to SC-administered treatments. We assessed the bioequivalence and safety of the citrate-free (CF) and original formulations of mirikizumab.</p><p><strong>Methods: </strong>The formulations were assessed in three phase 1, two-arm, randomized, single-dose, parallel design studies in healthy participants: study A (NCT04548219), study B (NCT05515601), and study C (NCT05644353). Participants were randomized 1:1 to either formulation, then further randomized to injection site locations of abdomen, arm, or thigh. The relative bioavailability (RBA) study A had a primary objective of assessing the RBA of a single 200 mg dose. Bioequivalence (BE) studies B and C had the primary objective of assessing the BE of a 200 and 300 mg dose, respectively. In all studies, the primary endpoints were C_max, AUC(0-∞), and AUC(0-t_last). The secondary objective was to assess safety and tolerability by treatment-emergent adverse events and serious adverse events. In study A, ISP was quantified prospectively using the 100-mm validated visual analogue scale (VAS) assessment form.</p><p><strong>Results: </strong>The primary objective was met in all studies. The RBA study found no significant difference in exposure between the formulations. BE was demonstrated between CF and original mirikizumab in both BE studies, with the 90% confidence intervals of the ratios of geometric least squares means within the pre-specified equivalence limits of 0.80 and 1.25. The frequency of ISP and injection site reactions (ISRs) was lower for CF than original mirikizumab in all studies. Furthermore, a significant difference in mean VAS score was observed in study A.</p><p><strong>Conclusion: </strong>Mirikizumab CF and original formulations were bioequivalent. The CF formulation was associated with less pain and fewer ISRs, with no other notable differences in safety profiles.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier NCT04548219, NCT05515601, NCT05644353.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Up-to-Date Description of the Use of Non-steroidal Anti-inflammatory Drugs (NSAIDs) in Italy: Evidence from Real Clinical Practice.","authors":"Valentina Perrone, Chiara Veronesi, Maria Ciappetta, Domenico Lucatelli, Andrea Cinti Luciani, Luca Degli Esposti","doi":"10.1007/s12325-025-03153-3","DOIUrl":"https://doi.org/10.1007/s12325-025-03153-3","url":null,"abstract":"<p><strong>Introduction: </strong>The prescription of non-steroidal anti-inflammatory drugs (NSAIDs) covered by the Italian National Health Service is limited to certain pathologies defined in the 2018 update of Note 66 of the Italian Medicines Agency (AIFA), meant to ensure appropriate use of NSAIDs. This analysis was conducted in real clinical practice to describe NSAID utilization from 2019 to 2022 with respect to Note 66 update.</p><p><strong>Methods: </strong>For this real-world analysis, data were extracted from the administrative databases of healthcare institutions covering ~ 9.1 million citizens. From 2019 to 2022, all subjects with ≥ 1 NSAID prescription were identified. Demographic and clinical characteristics, the proportion of NSAID-treated patients over time, the most prescribed molecules, and drug consumption defined as daily dose (DDD) per 1000 inhabitants/day were recorded.</p><p><strong>Results: </strong>The percentage NSAID-treated patients showed a slight increase over time (1.9-3.0%). The most prescribed active ingredients were diclofenac, ketoprofen, nimesulide, etoricoxib, and ibuprofen. NSAID consumption increased from 15.5 to 16.8 DDD/1000 inhabitants/day over 2020-2022, especially in older patients (65-74 years group: 36.2-39.3 DDD/1000 inhabitants/day). From 2019 to 2022, 2,811,910 patients with NSAID prescription(s) in Note 66 were identified, whose average age was 59.7 years. Among them, 0.1-1.0% received NSAIDs for rheumatic diseases and 11.9% in the oncological setting. While diclofenac, etoricoxib, and ketoprofen were commonly prescribed at medium-low dosage as recommended, ibuprofen was used at high dosage (600 mg) in 80% of cases.</p><p><strong>Conclusion: </strong>The analysis showed that patients prescribed with NSAIDs were relatively young (~ 60 years), in contrast with the pathologies covered by Note 66, which typically affect elderly people. Moreover, rheumatic and oncological diseases were poorly represented, thus it is possible that NSAIDs might have been prescribed for indications outside the note. These findings suggest that the use of NSAIDs for pain management in Italy should be optimized, properly weighting their risks and benefits.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention and Treatment of Intraoperative Complications During Gynecological Laparoscopic Surgery: Practical Tips and Tricks-A Narrative Review.","authors":"Matteo Giorgi, Giorgia Schettini, Luca La Banca, Alberto Cannoni, Alessandro Ginetti, Irene Colombi, Nassir Habib, Ramon Rovira, Francesco Martire, Lucia Lazzeri, Errico Zupi, Gabriele Centini","doi":"10.1007/s12325-025-03165-z","DOIUrl":"https://doi.org/10.1007/s12325-025-03165-z","url":null,"abstract":"<p><p>Several complications can occur during laparoscopic gynecological surgery. The insertion of trocars and the induction of pneumoperitoneum are essential steps, but they can still pose potential risks during laparoscopic surgery. Bowel injuries are the most common during gynecological procedures as a result of thermal damage and trocar placement, while vessel injuries may carry a high mortality rate. Gynecologic surgeons should be aware of the risks associated with laparoscopic procedures and be able to prevent and treat potential complications. We conducted a literature search using three electronic databases (Pubmed/MEDLINE, Google Scholar, Embase) from inception to May 2024 to identify the most common intraoperative gynecological laparoscopic complications, including those related to trocar insertion, bowel, urinary, and vessel injury. The aim of this narrative review is to describe the most common complications during gynecological laparoscopic surgery and to outline the safety rules and techniques necessary for their prevention and treatment.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Noninterventional, Cross-Sectional Study to Assess Patient Prostate Cancer Treatment Preferences and Experiences in Europe.","authors":"Emmanuelle Kaltenbach, Ana Maria Rodriguez-Leboeuf, Patrick Cabri, Mickael Henry-Szatkowski, Mehmet Inceer, Emma Karim, Valérie Perrot, Giuseppe Fallara, Matteo Ferro","doi":"10.1007/s12325-025-03152-4","DOIUrl":"https://doi.org/10.1007/s12325-025-03152-4","url":null,"abstract":"<p><strong>Introduction: </strong>Gonadotropin-releasing hormone (GnRH) agonist injection frequency does not affect prostate cancer treatment efficacy; however, it may influence treatment satisfaction, adherence, and overall healthcare utilization. This study addressed the limited information available on real-world patient experience with GnRH treatments by surveying a diverse population of patients with prostate cancer in Europe.</p><p><strong>Methods: </strong>This noninterventional, cross-sectional study included adults with locally advanced or metastatic prostate cancer in Belgium, France, Italy, Spain, and the UK. Data were collected via a one-time self-administered electronic survey (October-December 2023) that assessed patient preferences for injection frequency, satisfaction, healthcare resource utilization, and involvement in treatment decision-making.</p><p><strong>Results: </strong>Of 414 participants, 53.9% preferred a 6-month injection frequency, while 27.3% preferred a 3-month frequency. Among those receiving injections every 6 months, 77.0% were satisfied; 62.7% of those receiving injections every 3 months were satisfied. Two-thirds of participants (65.7%) were aware of different frequencies of injections. Among those who preferred a 3-month injection frequency, routine and perceived control over their disease were important factors, with 38.1% receiving injections at the same frequency as doctor visits. Among those preferring a 6-month frequency, convenience and routine were important; however, 7.2% indicated that their preference was based on a dislike or fear of injections. Of those with no preference, 60.3% indicated that this was because they deferred to their doctor's advice. Most patients required transport to their injection appointment, and of those who were employed, 79.2% required time off from work. Accompaniment to an injection appointment was also important, with 66.2% of patients never attending alone.</p><p><strong>Conclusion: </strong>The high satisfaction rates, particularly among those receiving injections every 6 months, suggest that less-frequent injections may be more convenient and preferable for many patients. These insights can help to guide patient-centric care and treatment decisions in prostate cancer management.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study.","authors":"Patricio Molero, Angela Ibañez, Javier de Diego-Adeliño, J Antoni Ramos-Quiroga, Marta García Dorado, Paola M López Rengel, Pilar A Saiz","doi":"10.1007/s12325-025-03149-z","DOIUrl":"https://doi.org/10.1007/s12325-025-03149-z","url":null,"abstract":"<p><strong>Introduction: </strong>The INTEGRATE study aimed to provide information on the use, effectiveness, and safety of esketamine nasal spray (ESK-NS) for the treatment of treatment-resistant depression (TRD) in real-world practice in Spain.</p><p><strong>Methods: </strong>This was an observational, cross-sectional, retrospective study conducted in adults aged 18-74 years who met the criteria for TRD. The weekly impact of ESK-NS on depressive symptoms was evaluated by clinical judgment using four categories (nonresponse, response, remission, not available). The onset of action 24 h after administration was also evaluated. Information on adverse events was collected from the medical records.</p><p><strong>Results: </strong>We included 196 patients, of whom 189 were considered evaluable; the mean (SD) number of previous episodes was 3.7 (3.0). According to the investigator's judgment, 152 (80.4%) of 189 patients were in response or remission in the induction phase, and 54 (90%) of 60 during the maintenance phase. The proportions of patients in remission were 9.5%, 18.7%, and 38.3% during the induction, optimization, and maintenance phases, respectively. Fifty-three (28.0%) patients experienced an improvement in depressive symptoms within the first 24 h after the first administration of ESK-NS. Most adverse events reported with ESK-NS were mild and did not require any action with the study drug; the number of adverse events decreased over time, especially during the first 4 weeks.</p><p><strong>Conclusion: </strong>Consistent with the available evidence, the results of this study indicate that ESK-NS is an effective and safe option to consider within the therapeutic algorithm for TRD.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PACAP: Beyond Migraine to Cluster, Menstrual, and Post-traumatic Headaches.","authors":"Lanfranco Pellesi, Mona Ameri Chalmer, Song Guo, Thien Phu Do, Zheman Xiao, Paolo Martelletti","doi":"10.1007/s12325-025-03166-y","DOIUrl":"https://doi.org/10.1007/s12325-025-03166-y","url":null,"abstract":"<p><p>The pituitary adenylate cyclase-activating peptide (PACAP) pathway is a critical focus in the pathophysiology of several headache disorders. PACAP influences headache pathophysiology through interactions with distinct receptors (PAC₁, VPAC₁, and VPAC₂) and pathways linked to neurovascular and hormonal regulation. Evidence supports its role in the modulation of trigeminal and parasympathetic systems, implicated in cluster headaches and menstrual migraine, and its involvement in sensitizing pain pathways post trauma in post-traumatic headaches. Early clinical trials targeting PACAP signaling show promise, with one study demonstrating efficacy in migraine prophylaxis. This narrative review synthesizes current evidence while addressing gaps in understanding PACAP's precise mechanisms. Future research should prioritize expanding the scope of PACAP-focused investigations across diverse headache types, aiming to establish it as a therapeutic target for several headache disorders. Success in ongoing and future trials could redefine headache management for millions of underserved patients worldwide.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Tablet Combination Therapy of Macitentan/Tadalafil for Patients with Pulmonary Arterial Hypertension: Qualitative Interview Study of the A DUE Phase 3 Trial.","authors":"Fenling Fan, Stacy Davis, Claire Burbridge, Kelly Chin, Michael Friberg, Ekkehard Grünig, Melanie Hughes, Pavel Jansa, Jörg Linder, Jennifer Rafalski, Alvaro Agustin Rodriguez, Jason A Randall","doi":"10.1007/s12325-025-03159-x","DOIUrl":"https://doi.org/10.1007/s12325-025-03159-x","url":null,"abstract":"<p><strong>Introduction: </strong>This study explored patient and clinician perspectives on a new fixed-dose combination of macitentan and tadalafil (M/T FDC) in a once-daily single tablet for treatment of pulmonary arterial hypertension (PAH).</p><p><strong>Methods: </strong>Qualitative semi-structured interviews were conducted during the open-label period of the global, phase 3 A DUE clinical trial that evaluated M/T FDC. A subset of enrolled patients (N = 26) and site investigators (N = 18 clinicians) were interviewed. Patients received four tablets during double-blind treatment and could be in one of three arms (macitentan + placebo; tadalafil + placebo; M/T FDC + placebo) followed by M/T FDC (one tablet) during the open-label period. Patients and clinicians were asked to share their experience of pre-trial PAH medication, double-blind treatment, and open-label M/T FDC. Thematic analysis was conducted on blinded data.</p><p><strong>Results: </strong>Patients preferred the M/T FDC tablet (open-label) over the four tablets during double-blind treatment. Patients were satisfied with M/T FDC, highlighting its positive impact on their psychological well-being, through reducing stress associated with managing multiple pills. All patients indicated that having a single, once-a-day pill for PAH was more convenient and associated with greater treatment adherence. Clinicians highlighted that their patients have a high daily pill burden for PAH and other comorbidities, and prefer treatments with an oral mode of administration that reduce the number of daily pills required. Clinicians felt that M/T FDC would be well received in clinical practice and potentially assist in implementing guideline-recommended combination treatment of PAH.</p><p><strong>Conclusions: </strong>In this qualitative analysis, all 26 patients and 18 clinicians provided positive feedback on M/T FDC treatment, which was consistent across countries. Reducing the number of pills needed to treat PAH, through use of single-tablet M/T FDC, is highly valued by patients and endorsed by clinicians, who both felt the single-tablet combination therapy could have a positive effect on patients' well-being and increase treatment adherence.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-306.","authors":"Jianming Xu, Ken Kato, Richard Hubner, Sook Ryun Park, Takashi Kojima, Ryu Ishihara, Lucjan Wyrwicz, Eric Van Cutsem, Paula Jimenez-Fonseca, Hongqian Wu, Lei Wang, Sebastian Yan, Jingwen Shi, Alysha Kadva, Harry H Yoon","doi":"10.1007/s12325-025-03115-9","DOIUrl":"https://doi.org/10.1007/s12325-025-03115-9","url":null,"abstract":"<p><strong>Introduction: </strong>The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against the use of programmed cell death protein-1 inhibitors for first-line treatment of advanced or metastatic unresectable esophageal squamous cell carcinoma (ESCC) with a programmed death-ligand 1 (PD-L1) expression Tumor Area Positivity (TAP) score < 1% or combined positive score < 1 due to an unfavorable benefit-risk profile observed across the phase 3 CheckMate 648, KEYNOTE-590, and RATIONALE-306 trials. Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.</p><p><strong>Methods: </strong>Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC. Efficacy and safety outcomes were evaluated among patients who were retrospectively assessed for PD-L1 expression defined by a TAP score ≥ 1%.</p><p><strong>Results: </strong>At primary analysis data cutoff (February 28, 2022), a clinically meaningful improvement in median overall survival was observed among 230 patients in the tislelizumab plus ICC arm {16.8 [95% confidence interval (CI) 15.3-20.8] months} versus 248 patients in the placebo plus ICC arm [9.6 (95% CI 8.9-11.8) months] [stratified hazard ratio 0.64 (95% CI 0.51-0.80)]; this was maintained at a 3-year follow-up data cutoff (November 24, 2023). Similar findings at primary analysis were observed for progression-free survival, objective response rate, disease control rate, and duration of response. Tislelizumab plus ICC was tolerable and no new safety signals were observed.</p><p><strong>Conclusions: </strong>Tislelizumab plus ICC is an effective and well tolerated first-line treatment option for patients with advanced or metastatic unresectable ESCC and a tumor PD-L1 TAP score ≥ 1%.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov NCT03783442.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}