ACS Omega最新文献

{"title":"Regulatory Fate of Cancer Indications in the European Union After Accelerated Approval in the US","authors":"Tonny Studsgaard Petersen, Kristian Karstoft, Freja Karuna Hemmingsen Sørup, Marie Lund, Allan Cramer","doi":"10.1001/jamaoncol.2024.5145","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5145","url":null,"abstract":"This cohort study investigates the regulatory fate in the European Union for drugs that received accelerated approval for cancer indications in the US.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"24 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer","authors":"Ying Cheng, Wei Zhang, Lin Wu, Caicun Zhou, Donglin Wang, Bing Xia, Minghong Bi, Xiuhua Fu, Chong Li, Dongqing Lv, Yanqiu Zhao, Gongyan Chen, Tienan Yi, Jianan Huang, Min Li, Runxiang Yang, Xiaoping Huang, Ye Wang, Mingjun Zhang, Yueyin Pan, Yilan Sun, Sheng Hu, Xiqin Zhang, Min Zhou, Jian Fang, Faguang Jin, Yunpeng Liu, Yinyin Li, Zhihong Zhang, Jie Hu, Laiyu Liu, Rui Wang, Yan Li, Kangsheng Gu, Cuimin Ding, Qingxia Fan, Guojun Zhang, Yongxing Chen, Liyan Jiang, Wei-E. Zheng, Shaoshui Chen, Cheng Huang, Zhigang Han, Hong Yang, Jianfang Wang, Baocheng Wang, Huita Wu, Yongxing Bao, Manxiang Li, Xianming Luo, Shanshan Gu, Wenbo Yu, Kai Xu, Simo Zhang, Jianjun Yu","doi":"10.1001/jamaoncol.2024.5019","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5019","url":null,"abstract":"ImportancePatients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.ObjectiveTo evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.Design, Setting, and ParticipantsThis multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China. Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC. Data were analyzed between May 6, 2023, and June 1, 2024.InterventionsPatients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.Main Outcomes and MeasuresThe primary end points were investigator-assessed progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.ResultsAmong 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP. By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months. Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio [HR], 0.67 [95% CI, 0.54-0.82]; <jats:italic>P</jats:italic> < .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; <jats:italic>P</jats:italic> = .03). The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group. Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, <jats:italic>HLA-A11<jats:sup>+</jats:sup> HLA-B62</jats:italic><jats:sup>−</jats:sup> haplotype, wild-type <jats:italic>KMT2D</jats:italic> and <jats:italic>COL4A4</jats:italic>, or sequence variations in <jats:italic>CTNNA2 or SCN4A</jats:italic> correlated with favorable PFS and OS in the toripalimab group. No new safety signals were observed. Grade 3 or higher treatment-emergent adverse event incidence was similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).Conclusions and RelevanceIn this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC. The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xl","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"36 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Global Pharmacoequity in Oncology","authors":"Parsa Erfani, Ruth L. Okediji, Vivienne Mulema, Edward R. Scheffer Cliff, Kwanele Asante-Shongwe, Brittany L. Bychkovksy, Temidayo Fadelu","doi":"10.1001/jamaoncol.2024.5032","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5032","url":null,"abstract":"ImportanceLimited availability and affordability of cancer drugs contribute to staggering disparities in cancer survival between high-income and low- and middle-income countries (LMICs). As infrastructure for cancer care rapidly develops, there is an urgent need to reduce prices and improve access to cancer medicines in LMICs to advance pharmacoequity globally.ObservationsPrior strategies to expand access to cancer medicines in LMICs have primarily relied on charity or differential pricing and have yielded limited results. Policymakers at the World Health Assembly recently proposed several strategies to increase global access to cancer drugs. Reviewing empirical data and lessons learned from medication access programs for HIV, COVID-19, and other infectious diseases, 3 strategies that multilateral organizations can use to reduce prices of cancer drugs in LMICs are discussed herein. These include (1) building regional technology transfer and manufacturing hubs, (2) expanding and streamlining use of compulsory licenses, and (3) implementing global standards for drug price transparency. Counterpoints to the critiques of these policies are critiqued and how programs can use these strategies to build on existing disease-centered initiatives is discussed.Conclusions and RelevanceLessons learned from the global response to HIV and COVID-19 show that international collaboration and support from the World Health and Trade Organizations can ensure a unified, coordinated agenda for advancing access to care in LMICs. Building on these lessons and implementing similar approaches for cancer drugs can play a critical role in expanding accessibility and affordability of cancer medicines in LMICs. With a growing burden of cancer morbidity and mortality in LMICs, redoubled efforts to deliver essential cancer medications to LMICs would have an immense impact on global cancer control and achieving the United Nations Sustainable Development Goals.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"37 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grief-Specific Cognitive Behavioral Therapy vs Present-Centered Therapy","authors":"Rita Rosner, Jörn Rau, Anette Kersting, Winfried Rief, Regina Steil, Anna-Maria Rummel, Anna Vogel, Hannah Comtesse","doi":"10.1001/jamapsychiatry.2024.3409","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3409","url":null,"abstract":"ImportanceProlonged grief disorder (PGD) is included as a new diagnosis in international classification systems. Treatments following a cognitive behavioral model are most effective, but comparisons with active control treatments are scarce.ObjectiveTo examine whether integrative cognitive behavioral therapy for prolonged grief (PG-CBT) is superior to present-centered therapy (PCT).Design, Setting, and ParticipantsThis was a rater-blinded, multicenter, randomized clinical trial (stratified by center and relationship to the deceased) with enrollment from April 2017 to May 2022. The setting included 4 university outpatient clinics in Germany. Eligible participants were aged 18 to 75 years and had PGD based on the Prolonged Grief Disorder 13 (PG-13) interview. Participants were randomized 1:1 to PG-CBT and PCT.InterventionsPG-CBT focused on the exposure to the worst moment of the loss and cognitive restructuring of grief-related cognitions in combination with solution-focused and experiential methods (eg, walk to the grave exercise). PCT was adapted in session length and number to PG-CBT and focused on a supportive relationship and coping with daily problems that may have arisen from the loss or grief symptoms.Main Outcomes and MeasuresAll outcomes were assessed at baseline, after treatment, and 12 months after randomization at follow-up. The primary outcome was a blinded assessment of the PG-13 severity score at follow-up. Secondary outcomes were self-reported depressive, somatic, and overall psychopathological symptoms.ResultsOf 544 treatment-seeking individuals experiencing bereavement, 212 eligible participants (mean [SD] age, 51.8 [13.3] years; 173 female [82%]) with PGD based on the PG-13 interview were randomized to PG-CBT and PCT (n = 106 in each condition). In the intention-to-treat analysis, both treatments yielded high reductions in PGD severity at follow-up (PG-CBT: Cohen <jats:italic>d</jats:italic> = 1.64; 95% CI, 1.31-1.97; PCT: Cohen <jats:italic>d</jats:italic> = 1.38; 95% CI, 1.09-1.66). After treatment, participants receiving PG-CBT demonstrated significantly greater reductions in PGD severity than those receiving PCT (Cohen <jats:italic>d</jats:italic> = 0.31; 95% CI, 0.03-0.57). At follow-up, this effect was only visible on a trend level (Cohen <jats:italic>d</jats:italic> = 0.28; 95% CI, −0.02 to 0.57), whereas participants in the PG-CBT group had significantly less depressive and general psychopathological symptoms. Twenty-three participants (20%) discontinued PG-CBT treatment, and 17 participants (16%) discontinued PCT.Conclusion and RelevanceThis randomized clinical trial demonstrates that PG-CBT was superior to PCT after treatment and at follow-up with regard to comorbid symptoms. Both treatments were shown to be effective and acceptable, showing the potential for dissemination and increasing patient choice.Trial registrationGerman Clinical Trials Register (DRKS) identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/199","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"22 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder","authors":"Daniel T. Myran, Michael Pugliese, Jennifer Xiao, Tyler S. Kaster, M. Ishrat Husain, Kelly K. Anderson, Nicholas Fabiano, Stanley Wong, Jess G. Fiedorowicz, Colleen Webber, Peter Tanuseputro, Marco Solmi","doi":"10.1001/jamapsychiatry.2024.3532","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3532","url":null,"abstract":"ImportanceInterest in and use of hallucinogens has been increasing rapidly. While a frequently raised concern is that hallucinogens may be associated with an increased risk of psychosis, there are limited data on this association.ObjectivesTo examine whether individuals with an emergency department (ED) visit involving hallucinogen use have an increased risk of developing a schizophrenia spectrum disorder (SSD).Design, Settings, and ParticipantsThis population-based, retrospective cohort study (January 2008 to December 2021) included all individuals aged 14 to 65 years in Ontario, Canada, with no history of psychosis (SSD or substance induced). Data were analyzed from May to August 2024.ExposureAn incident ED visit involving hallucinogen use.Main Outcomes and MeasuresDiagnosis of SSD using a medical record–validated algorithm. Associations between ED visits involving hallucinogens and SSD were estimated using cause-specific adjusted hazard models. Individuals with an incident ED visit involving hallucinogens were compared with members of the general population (primary analysis) or individuals with ED visits involving alcohol or cannabis (secondary analysis).ResultsThe study included 9 244 292 individuals (mean [SD] age, 40.4 [14.7] years; 50.2% female) without a history of psychosis, with a median follow-up of 5.1 years (IQR, 2.3-8.6 years); 5217 (0.1%) had an incident ED visit involving hallucinogen use. Annual rates of incident ED visits involving hallucinogens were stable between 2008 and 2012 and then increased by 86.4% between 2013 and 2021 (3.4 vs 6.4 per 100 000 individuals). Individuals with ED visits involving hallucinogens had a greater risk of being diagnosed with an SSD within 3 years compared with the general population (age- and sex-adjusted hazard ratio [HR], 21.32 [95% CI, 18.58-24.47]; absolute proportion with SSD at 3 years, 208 of 5217 with hallucinogen use [3.99%] vs 13 639 of 9 239 075 in the general population [0.15%]). After adjustment for comorbid substance use and mental health conditions, individuals with hallucinogen ED visits had a greater risk of SSD compared with the general population (HR, 3.53; 95% CI, 3.05-4.09). Emergency department visits involving hallucinogens were associated with an increased risk of SSD within 3 years compared with ED visits involving alcohol (HR, 4.66; 95% CI, 3.82-5.68) and cannabis (HR, 1.47; 95% CI, 1.21-1.80) in the fully adjusted model.Conclusions and RelevanceIn this cohort study, individuals with an ED visit involving hallucinogen use had a greater risk of developing an SSD compared with both the general population and with individuals with ED visits for other types of substances. These findings have important clinical and policy implications given the increasing use of hallucinogens and associated ED visits.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"70 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder","authors":"Markku Lähteenvuo, Jari Tiihonen, Anssi Solismaa, Antti Tanskanen, Ellenor Mittendorfer-Rutz, Heidi Taipale","doi":"10.1001/jamapsychiatry.2024.3599","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3599","url":null,"abstract":"ImportancePreliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption.ObjectiveTo test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual.Design, Setting, and ParticipantsThis cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD.ExposuresThe primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD.Main Outcomes and MeasuresThe primary outcome was AUD hospitalization analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)–related hospitalization, somatic hospitalization, and suicide attempt.ResultsThe cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15).Conclusions and RelevanceAmong patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"11 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic Density in Early Stages of Psychosis and Clinical High Risk","authors":"M. Belen Blasco, Kankana Nisha Aji, Christian Ramos-Jiménez, Ilana Ruth Leppert, Christine Lucas Tardif, Johan Cohen, Pablo M. Rusjan, Romina Mizrahi","doi":"10.1001/jamapsychiatry.2024.3608","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3608","url":null,"abstract":"ImportanceSynaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.ObjectiveTo investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.Design, Setting, and ParticipantsThis cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).Main Outcomes and MeasuresSynaptic density was quantified with dynamic 90-minute [<jats:sup>18</jats:sup>F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.ResultsA total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (<jats:italic>F</jats:italic><jats:sub>2,273</jats:sub> = 4.02, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.17; ROI: <jats:italic>F</jats:italic><jats:sub>5,273</jats:sub> = 360.18, <jats:italic>P</jats:italic> < .01, Cohen <jats:italic>F</jats:italic> = 2.55) with a group × ROI interaction (<jats:italic>F</jats:italic><jats:sub>10,273</jats:sub> = 2.67, <jats:italic>P</jats:italic> < .01, Cohen <jats:italic>F</jats:italic> = 0.32). Synaptic density was lower in cannabis users (<jats:italic>F</jats:italic><jats:sub>1,272</jats:sub> = 5.31, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: <jats:italic>F</jats:italic><jats:sub>1,81</jats:sub> = 4.31, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.23; Scale of Psychosis-Risk Symptoms negative scores: <jats:italic>F</jats:italic><jats:sub>1,90</jats:sub> = 4.12, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.21). SV2A binding potential was significantly associated with neurite density index (<jats:italic>F</jats:italic><jats:sub>1,138</jats:sub> = 6.76, <jats:italic>P</jats:italic> = .01, Cohen <jats:italic>F</jats:italic> = 0.22).Con","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"44 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Adverse Effects and Complications After Prostate Cancer Treatment","authors":"Joseph M. Unger, Cathee Till, Catherine M. Tangen, Dawn L. Hershman, Phyllis J. Goodman, Michael LeBlanc, William E. Barlow, Riha Vaidya, Lori M. Minasian, Howard L. Parnes, Ian M. Thompson","doi":"10.1001/jamaoncol.2024.4397","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4397","url":null,"abstract":"ImportanceDue to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities.ObjectiveTo characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males.Design, Setting, and ParticipantsThis cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024.ExposureProstatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records.Main Outcomes and MeasuresTen potential PCA treatment-related complications identified from Medicare claims data.ResultsThe study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; <jats:italic>P </jats:italic>&amp;amp;lt; .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; <jats:italic>P </jats:italic>&amp;amp;lt; .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; <jats:italic>P </jats:italic>&amp;amp;lt; .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; <jats:italic>P </jats:italic>&amp;amp;lt; .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; <jats:italic>P </jats:italic>&amp;amp;lt; .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.Conclusions and RelevanceThis cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"3 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma","authors":"Chunrui Li, Keshu Zhou, Yongxian Hu, Dehui Zou, Lijuan Chen, Bing Chen, Jing Liu, Xi Zhang, Hanyun Ren, Kai Hu, Peng Liu, Jian-Qing Mi, Zhenyu Li, Kaiyang Ding, Di Wang, Wen Wang, Songbai Cai, Jianyong Li, Yongping Song, He Huang, Lugui Qiu","doi":"10.1001/jamaoncol.2024.4879","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4879","url":null,"abstract":"ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 10<jats:sup>6</jats:sup> CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10<jats:sup>−5</jats:sup>. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.chictr.org.cn/showproj.html?proj=53503\">ChiCTR2000033946</jats:ext-link>","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"196 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Financial Toxicity Among Asian American Cancer Survivors","authors":"Stephanie Wang, Fumiko Chino, Edward Christopher Dee","doi":"10.1001/jamaoncol.2024.5016","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5016","url":null,"abstract":"This Viewpoint highlights financial toxicity specific to Asian American cancer survivors and presents steps forward within the framework of the social ecological model of health, considering individual, interpersonal, community, and policy-level dimensions.","PeriodicalId":22,"journal":{"name":"ACS Omega","volume":"18 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}