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Unaffordable housing and cancer: novel insights into a complex question. 负担不起的住房与癌症:对复杂问题的新见解。
IF 4.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae029
Caroline A Thompson, Roch A Nianogo, Tammy Leonard
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引用次数: 0
RE: A predictive model for lung cancer screening nonadherence in a community setting healthcare network. RE:社区医疗网络中肺癌筛查不依从性的预测模型。
IF 4.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae040
Yannan Lin, Ruiwen Ding, Panayiotis Petousis, Ashley Elizabeth Prosper, Denise R Aberle, William Hsu
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引用次数: 0
Severe housing cost burden and premature mortality from cancer. 严重的住房成本负担和癌症导致的过早死亡。
IF 4.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae011
Wayne R Lawrence, Neal D Freedman, Jennifer K McGee-Avila, Lee Mason, Yingxi Chen, Aldenise P Ewing, Meredith S Shiels

Unaffordable housing has been associated with poor health. We investigated the relationship between severe housing cost burden and premature cancer mortality (death before 65 years of age) overall and by Medicaid expansion status. County-level severe housing cost burden was measured by the percentage of households that spend 50% or more of their income on housing. States were classified on the basis of Medicaid expansion status (expanded, late-expanded, nonexpanded). Mortality-adjusted rate ratios were estimated by cancer type across severe housing cost burden quintiles. Compared with the lowest quintile of severe housing cost burden, counties in the highest quintile had a 5% greater cancer mortality rate (mortality-adjusted rate ratio = 1.05, 95% confidence interval = 1.01 to 1.08). Within each severe housing cost burden quintile, cancer mortality rates were greater in states that did not expand Medicaid, though this association was significant only in the fourth quintile (mortality-adjusted rate ratio = 1.08, 95% confidence interval = 1.03 to 1.13). Our findings demonstrate that counties with greater severe housing cost burden had higher premature cancer death rates, and rates are potentially greater in non-Medicaid-expanded states than Medicaid-expanded states.

负担不起的住房与健康状况不佳有关。我们研究了严重住房成本负担(SHCB)与癌症过早死亡率(死亡人数)之间的关系。
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引用次数: 0
Addressing social needs in oncology care: another research-to-practice gap. 满足肿瘤治疗中的社会需求:从研究到实践的另一个差距。
IF 4.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae032
Emily Haines, Rachel C Shelton, Kristie Foley, Rinad S Beidas, Emily V Dressler, Carol A Kittel, Krisda H Chaiyachati, Oluwadamilola M Fayanju, Sarah A Birken, Daniel Blumenthal, Katharine A Rendle

Social determinants of health and unmet social needs are directly related to cancer outcomes, from diagnosis to survivorship. If identified, unmet social needs can be addressed in oncology care by changing care plans in collaboration with patients' preferences and accounting for clinical practice guidelines (eg, reducing the frequency of appointments, switching treatment modalities) and connecting patients to resources within healthcare organizations (eg, social work support, patient navigation) and with community organizations (eg, food banks, housing assistance programs). Screening for social needs is the first step to identifying those who need additional support and is increasingly recognized as a necessary component of high-quality cancer care delivery. Despite evidence about the relationship between social needs and cancer outcomes and the abundance of screening tools, the implementation of social needs screening remains a challenge, and little is known regarding the adoption, reach, and sustainability of social needs screening in routine clinical practice. We present data on the adoption and implementation of social needs screening at two large academic cancer centers and discuss three challenges associated with implementing evidence-based social needs screening in clinical practice: (1) identifying an optimal approach for administering social needs screening in oncology care, (2) adequately addressing identified unmet needs with resources and support, and (3) coordinating social needs screening between oncology and primary care.

健康的社会决定因素和未满足的社会需求与癌症从诊断到存活的结果直接相关。如果能识别出未满足的社会需求,就可以在肿瘤治疗过程中根据患者的偏好和临床实践指南改变治疗计划(如减少预约次数、改变治疗方式),并将患者与医疗机构内的资源(如社会工作支持、患者指导)和社区组织(如食物银行、住房援助计划)联系起来,从而解决未满足的社会需求。社会需求筛查是识别需要额外支持的患者的第一步,也被越来越多的人认为是提供高质量癌症护理的必要组成部分。尽管有证据表明社会需求与癌症预后之间存在关系,而且筛查工具也很丰富,但社会需求筛查的实施仍是一项挑战,人们对社会需求筛查在常规临床实践中的采用、覆盖范围和可持续性知之甚少。我们介绍了两个大型学术癌症中心采用和实施社会需求筛查的数据,并讨论了在临床实践中实施循证社会需求筛查所面临的三个挑战:(1)确定在肿瘤护理中实施社会需求筛查的最佳方法;(2)通过资源和支持充分满足已确定的未满足需求;(3)协调肿瘤和初级护理之间的社会需求筛查。
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引用次数: 0
Financial-legal navigation reduces financial toxicity of pediatric, adolescent, and young adult cancers. 财务-法律导航可降低儿科癌症和亚健康癌症的财务毒性。
IF 4.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae025
Jean Edward, Kimberly D Northrip, Mary Kay Rayens, Andrea Welker, Rachel O'Farrell, Jennifer Knuf, Haafsah Fariduddin, Julia Costich, John D'Orazio

Background: Pediatric, adolescent, and young adult patients with cancer and their caregivers are at high risk of financial toxicity, and few evidence-based oncology financial and legal navigation programs exist to address it. We tested the feasibility, acceptability, and preliminary effectiveness of Financial and Insurance Navigation Assistance, a novel interdisciplinary financial and legal navigation intervention for pediatric, adolescent and young adult patients and their caregivers.

Methods: We used a single-arm feasibility and acceptability trial design in a pediatric hematology and oncology clinic and collected preintervention and postintervention surveys to assess changes in financial toxicity (3 domains: psychological response/Comprehensive Score for Financial Toxicity [COST], material conditions, and coping behaviors); health-related quality of life (Patient-Reported Outcomes Measurement Information System Physical and Mental Health, Anxiety, Depression, and Parent Proxy scales); and perceived feasibility, acceptability, and appropriateness.

Results: In total, 45 participants received financial navigation, 6 received legal navigation, and 10 received both. Among 15 adult patients, significant improvements in FACIT-COST (P = .041) and physical health (P = .036) were noted. Among 46 caregivers, significant improvements were noted for FACIT-COST (P < .001), the total financial toxicity score (P = .001), and the parent proxy global health score (P = .0037). We were able to secure roughly $335 323 in financial benefits for 48 participants. The intervention was rated highly for feasibility, acceptability, and appropriateness.

Conclusions: Integrating financial and legal navigation through Financial and Insurance Navigation Assistance was feasible and acceptable and underscores the benefit of a multidisciplinary approach to addressing financial toxicity.

Clinicaltrials.gov registration: NCT05876325.

背景:儿科和青少年癌症患者及护理人员是财务毒性的高危人群,而目前很少有循证的肿瘤财务和法律导航计划来解决这一问题。我们测试了 FINassist(财务和保险导航援助)的可行性、可接受性和初步有效性,这是一项针对儿科肿瘤患者和护理人员的新型跨学科财务和法律导航干预措施:我们在儿科肿瘤学和血液学部门采用了单臂可行性和可接受性试验设计,并收集了干预前后的调查问卷,以评估财务毒性(三个领域:心理反应/财务毒性综合评分[COST]、物质条件和应对行为)、与健康相关的生活质量(PROMIS 身心健康、焦虑、抑郁和家长代理量表)以及感知可行性、可接受性和适当性的变化:45 名参与者接受了财务指导,6 名接受了法律指导,10 名同时接受了财务和法律指导。15 名成年患者的 COST(P=0.041)和身体健康(0.036)均有显著改善。在 46 名护理人员中,COST 有明显改善(结论:通过 FINassist 将财务和法律指导结合起来是可行的、可接受的,并强调了采用多学科方法解决财务毒性问题的益处。
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引用次数: 0
Why location matters: associations between county-level characteristics and availability of National Cancer Oncology Research Program and National Cancer Institute sites. 为什么地点很重要?县级特征与 NCORP 和 NCI 站点可用性之间的关联。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae038
Nicole E Caston, Courtney P Williams, Emily B Levitan, Russell Griffin, Andres Azuero, Stephanie B Wheeler, Gabrielle B Rocque

Background: The majority of patients with cancer seek care at community oncology sites; however, most clinical trials are available at National Cancer Institute (NCI)-designated sites. Although the NCI National Cancer Oncology Research Program (NCORP) was designed to address this problem, little is known about the county-level characteristics of NCORP site locations.

Methods: This cross-sectional analysis determined the association between availability of NCORP or NCI sites and county-level characteristic theme percentile scores from the Center for Disease Control and Prevention's Social Vulnerability Index themes. Health Resources and Services Administration's Area Health Resource Files were used to determine contiguous counties. We estimated risk ratios and 95% confidence intervals (CIs) using modified Poisson regression models to evaluate the association between county-level characteristics and site availability within singular and singular and contiguous counties.

Results: Of 3141 included counties, 14% had an NCORP, 2% had an NCI, and 1% had both sites. Among singular counties, for a standard deviation increase in the racial and ethnic theme score, there was a 22% higher likelihood of NCORP site availability (95% CI = 1.10 to 1.36); for a standard deviation increase in the socioeconomic status theme score, there was a 24% lower likelihood of NCORP site availability (95% CI = 0.67 to 0.87). Associations were of smaller magnitude when including contiguous counties. NCI sites were located in more vulnerable counties.

Conclusions: NCORP sites were more often in racially diverse counties and less often in socioeconomically vulnerable counties. Research is needed to understand how clinical trial representation will increase if NCORP sites strategically increase their locations in more vulnerable counties.

背景:大多数癌症患者都在社区肿瘤医院接受治疗;然而,大多数临床试验都是在国家癌症研究所(NCI)指定的医院进行的。虽然美国国家癌症研究所(NCI)的国家癌症肿瘤研究计划(NCORP)旨在解决这一问题,但人们对国家癌症肿瘤研究计划地点的县级特征知之甚少:这项横断面分析确定了 NCORP 或 NCI 站点的可用性与县级特征主题百分位数(来自疾病预防控制中心的社会脆弱性指数主题)之间的关联。我们使用卫生资源与服务管理局的地区卫生资源档案来确定毗连县。我们使用修正的泊松回归模型估算了风险比和 95% 的置信区间 (CI),以评估单一县和单一及毗邻县的县级特征与场所可用性之间的关联:在纳入的 3141 个县中,14% 的县拥有 NCORP,2% 的县拥有 NCI,1% 的县同时拥有这两个站点。在单一县中,种族和民族主题得分每增加一个标准差 (SD),NCORP 站点可用性的可能性就会增加 22%(95% CI 1.10-1.36);社会经济地位主题得分每增加一个标准差,NCORP 站点可用性的可能性就会降低 24%(95% CI 0.67-0.87)。如果将毗连县也包括在内,则相关性较小。NCI站点位于更脆弱的县:NCORP研究机构更多位于种族多样化的县,而较少位于社会经济脆弱的县。需要开展研究,以了解如果 NCORP 机构战略性地增加其在弱势县的位置,临床试验的代表性将如何增加。
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引用次数: 0
A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis. 头颈部癌症患者心理健康的全面检查:系统回顾和荟萃分析。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae031
Pablo Jimenez-Labaig, Claudia Aymerich, Irene Braña, Antonio Rullan, Jon Cacicedo, Miguel Ángel González-Torres, Kevin J Harrington, Ana Catalan

Background: Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown.

Methods: A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology-compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors.

Results: A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress.

Conclusions: Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential.

背景:头颈部癌症(HNC)患者的情绪困扰尤为严重。然而,这一人群中与临床相关的精神健康症状和失调的实际发生率仍然未知:方法:我们进行了一项符合 PRISMA/MOOSE 标准的系统综述和定量随机效应荟萃分析,以确定该人群的自杀发生率以及抑郁、焦虑、痛苦、创伤后应激和失眠的患病率。研究人员检索了 MEDLINE、WebofScience、Cochrane Central Register、KCI-Korean Journal、SciELO、Russian Science Citation Index 和 Ovid/PsycINFO 等数据库,检索时间从数据库建立之初至 2023 年 8 月 1 日(PROSPERO:CRD42023441432)。结果:共发现 208 项研究(n = 654 413,中位年龄 60.7;25.5% 为女性)。19.5%的患者报告了抑郁症状(95%置信区间[CI]=17-21%),17.8%的患者报告了焦虑症状(95%CI=14-21%),34.3%的患者报告了痛苦症状(95%CI=29-39%),17.7%的患者报告了创伤后症状(95%CI=6-41%),43.8%的患者报告了失眠症状(95%CI=35-52%)。诊断标准评估显示,失调症的发病率较低:抑郁症占 10.3%(95%CI = 7-13%),焦虑症占 5.6%(95%CI = 2-10%),失眠症占 9.6%(95%CI = 1-40%),创伤后应激反应占 1%(95%CI = 0-84.5%)。自杀综合发病率为每年每 10 万人 161.16 例(95%CI = 82-239)。元回归发现,与手术相比,接受原发性化疗的患者的焦虑发生率具有显著的统计学意义,吸烟者和肿瘤分期晚期患者的焦虑发生率更高。欧洲样本的焦虑发生率较低:结论:HNC 患者在所有领域都存在严重的心理健康问题。自杀仍是一个高度相关的问题。符合标准的失调发生率明显低于临床相关症状。对症状严重的患者进行有针对性的失调症评估的有效性调查至关重要。
{"title":"A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis.","authors":"Pablo Jimenez-Labaig, Claudia Aymerich, Irene Braña, Antonio Rullan, Jon Cacicedo, Miguel Ángel González-Torres, Kevin J Harrington, Ana Catalan","doi":"10.1093/jncics/pkae031","DOIUrl":"10.1093/jncics/pkae031","url":null,"abstract":"<p><strong>Background: </strong>Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown.</p><p><strong>Methods: </strong>A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology-compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors.</p><p><strong>Results: </strong>A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress.</p><p><strong>Conclusions: </strong>Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The statistical significance revolution. 统计意义革命
IF 3.4 Q2 Medicine Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae035
Alfred I Neugut, Tito Fojo

Statistical significance has long relied on the criterion of P less than or equal to .05. Although this threshold has generally functioned well, it has engendered some negative practices to circumvent it and been criticized as too inflexible. We concur with the statisticians and methodologists who are currently arguing for more flexibility to the P value and more reliance on the 95% confidence interval, a shift that is likely to change future practice in data analysis and interpretation for oncology.

长期以来,统计意义一直依赖于 p
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引用次数: 0
Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield. 采用粪便免疫化学检验或初级结肠镜检查进行结直肠癌筛查:诊断率的不平等。
IF 3.4 Q2 ONCOLOGY Pub Date : 2024-04-30 DOI: 10.1093/jncics/pkae043
Carl Bonander, Marcus Westerberg, Gabriella Chauca Strand, Anna Forsberg, Ulf Strömberg

Background: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear.

Methods: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT.

Results: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT.

Conclusions: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups.

Clinical trial registration: ClinicalTrials.gov identifier NCT02078804.

背景:在接受结直肠癌筛查方面存在的社会经济不平等已被充分记录在案,但其对健康不平等的影响仍不清楚:在 2014 年 3 月至 2020 年 3 月期间,我们从瑞典人口中随机招募了 60 岁的人,并邀请他们接受间隔 2 年的粪便免疫化学检测 (FIT)(n = 60,137 人)或仅一次的初级结肠镜检查 (PCOL;n = 30,400 人)。通过与瑞典统计局登记处的链接,我们获得了社会经济数据。在每个确定的社会经济组中,我们估算了每个筛查组的晚期肿瘤(AN)累积发病率(意向筛查分析)。我们预测了第三轮 FIT 后 PCOL 组超过筛查率的概率:Pr{AN_FIT3>AN_PCOL}:结果:在最低收入组中,两轮 FIT 后 AN 感染率为 1.63%(95% 置信区间 [CI] = 1.35% 至 1.93%),而 PCOL 组为 1.93%(95% 置信区间 [CI] = 1.49% 至 2.40%)。我们预测 Pr{AN_FIT3>AN_PCOL} = 0.86。在最高收入组中,我们发现两种筛查策略的收益差距更为明显,分别为 2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%),且 Pr{AN_FIT3>AN_PCOL} 很低 (= 0.02)。(= 0.02):在社会经济地位较低的群体中,相隔 2 年的 FIT 和 PCOL 分别产生的 AN 值较低,但差异较小。这些结果对评估有组织的大肠癌筛查中的健康公平性很有价值:临床试验注册:ClinicalTrials.gov 编号 NCT02078804。
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引用次数: 0
Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations. Derazantinib单药与atezolizumab联合治疗FGFR畸变活化的转移性尿路上皮癌
IF 4.4 Q2 Medicine Pub Date : 2024-04-16 DOI: 10.1093/jncics/pkae030
Andrea Necchi, R. Ramlau, A. Falcón González, Arvind Chaudhry, Tilman Todenhöfer, R. Tahbaz, Elisa Fontana, P. Giannatempo, J. Deville, D. Pouessel, Shinkyo Yoon, Thomas Powles, Mathieu Bernat, M. Häckl, M. Marszewska, P. Mckernan, Mikael Saulay, Federica Scaleia, Marc Engelhardt, Y. Loriot, A. Siefker-Radtke, M. De Santis
BACKGROUNDThis Phase 1 b/2 study assessed the efficacy, in terms of objective response rate (ORR) of the FGFR1/2/3 kinase inhibitor derazantinib as monotherapy or in combination with atezolizumab in patients with metastatic urothelial cancer (mUC) and FGFR1-3 genetic aberrations (FGFR1-3GA).METHODSThis multicenter, open-label study comprised 5 substudies. In Substudies 1 and 5, patients with mUC with FGFR1-3GA received derazantinib monotherapy (300 mg QD in Substudy 1, 200 mg BID in Substudy 5). In Substudy 2, patients with any solid tumor received atezolizumab 1200 mg every 3 weeks plus derazantinib 200 or 300 mg QD. In Substudy 3, patients with mUC harboring FGFR1-3GA received derazantinib 200 mg BID plus atezolizumab 1200 mg every 3 weeks. In Substudy 4, patients with FGFR inhibitor-resistant mUC harboring FGFR1-3GA received derazantinib 300 mg QD monotherapy or derazantinib 300 mg QD plus atezolizumab 1200 mg every 3 weeks.RESULTSThe ORR for Substudies 1 and 5 combined was 4/49 (8.2%, 95% CI: 2.3, 19.6%), based on 4 partial responses. The ORR in Substudy 4 was 1/7 (14.3%, 95% CI: 0.4, 57.9%; 1 partial response for derazantinib 300 mg monotherapy, zero for derazantinib 300 mg plus atezolizumab 1200 mg). In Substudy 2, derazantinib 300 mg plus atezolizumab 1200 mg was identified as a recommended dose for Phase 2. Only 2 patients entered Substudy 3.CONCLUSIONSDerazantinib as monotherapy or in combination with atezolizumab was well-tolerated but did not show sufficient efficacy to warrant further development in mUC.
背景这项1 b/2期研究评估了FGFR1/2/3激酶抑制剂derazantinib单药治疗或与阿特珠单抗联合治疗转移性尿路上皮癌(mUC)和FGFR1-3基因畸变(FGFR1-3GA)患者的疗效,即客观反应率(ORR)。在子研究1和5中,伴有FGFR1-3GA的mUC患者接受了德氮替尼单药治疗(子研究1为300毫克QD,子研究5为200毫克BID)。在子研究2中,任何实体瘤患者均接受阿特珠单抗(atezolizumab)1200毫克,每3周一次,外加200或300毫克的德氮替尼(derazantinib)QD。在子研究3中,携带FGFR1-3GA的mUC患者每3周接受一次200毫克/日的德拉赞替尼加1200毫克的阿特佐利珠单抗治疗。在子研究4中,携带FGFR1-3GA的FGFR抑制剂耐药mUC患者接受了德氮替尼300 mg QD单药治疗或德氮替尼300 mg QD加阿特珠单抗1200 mg每3周一次的治疗。结果子研究1和5的ORR合计为4/49(8.2%,95% CI:2.3,19.6%),基于4个部分应答。子研究4的ORR为1/7(14.3%,95% CI:0.4,57.9%;德甘替尼300毫克单药治疗有1例部分应答,德甘替尼300毫克加阿特珠单抗1200毫克治疗无部分应答)。在次级研究2中,德扎替尼300毫克加阿特珠单抗1200毫克被确定为第二阶段的推荐剂量。只有2名患者进入了子研究3。结论德拉扎替尼单药治疗或与阿特珠单抗联合治疗的耐受性良好,但未显示出足够的疗效,不值得进一步开发mUC。
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引用次数: 0
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