亚临床甲状腺功能减退与甲状腺功能减退患者心脏结构及功能的改变

目的 观察亚临床甲状腺功能减退（SCH）和甲状腺功能减退（甲减）患者的超声心动图,分析其心脏结构与功能的改变。方法 选取2011年3月至2017年3月北京朝阳医院收治的58例SCH患者为SCH组,21例甲减患者为甲减组,选择同期甲状腺功能正常的健康体检者65例为对照组进行回顾性研究。比较3组对象超声心动图参数如左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）、左室射血分数、主动脉窦内径等的变化,并分析甲状腺功能状态对3组研究对象心脏结构与功能的影响。结果 对照组、SCH组及甲减组患者的LVEDD分别为（47.69±4.13）、（45.33±4.45）和（42.81±4.26）mm,3组差异有统计学意义（P<0.05）。对照组、SCH组及甲减组患者的LVESD分别为（29.69±3.34）、（27.45±4.16）和（26.48±3.89）mm,3组差异有统计学意义（P<0.05）。结论 SCH患者与甲状腺功能减退患者的LVEDD和LVESD减小,左心室功能降低。     

帕博利珠单抗致甲状腺功能障碍文献分析

目的 探索帕博利珠单抗致甲状腺功能障碍发生的规律和临床特点，为临床安全用药提供参考。方法 检索知网、维普、万方、PubMed、Web of Science数据库，收集关于帕博利珠单抗致免疫性皮肤病的文献数据并进行统计分析。结果 纳入16篇文献，共16例甲状腺功能障碍病例，年龄为30～77岁；甲状腺功能障碍发生时间最早为给药后14 d，最晚为给药后240 d；常规给予左甲状腺素治疗甲状腺功能减退及给予甲硫咪唑治疗甲状腺功能亢进，经过治疗后多数患者甲状腺功能障碍好转。结论 在使用帕博利珠单抗时要注意监测甲状腺功能障碍不良反应，一旦发生应及时进行相应治疗。     

甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的临床对照研究

目的探讨甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能影响的疗效。方法选取80例甲状腺功能亢进患者,随机分为两组,甲组（41例）口服甲巯咪唑,乙组（39例）口服丙硫氧嘧啶片。观察并记录两组患者治疗前后甲状腺功能指标,肝功能指标,肝功能受损情况及治疗期间不良反应情况,评价甲巯咪唑和丙硫氧嘧啶对甲状腺功能亢进患者肝功能的影响。结果治疗前,两组患者由于甲状腺功能亢进,三碘甲腺原氨酸（FT₃）、四碘甲腺原氨酸（FT₄）均处于高水平状态,且差异无统计学意义。促甲状腺激素（TSH）分泌受到抑制,处于较低水平。治疗后,患者甲状腺功能亢进症状有所改善,患者FT₃、FT₄较治疗前降低,TSH较治疗前升高（P<0.05）,但组间比较差异无统计学意义。治疗前,两组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷氨酰转肽酶（GGT）水平相比,差异无统计学意义。治疗后乙组ALT、AST、GGT水平均有所升高,并明显高于甲组（P<0.05）,其中,以ALT变化最为明显;甲组治疗前后无明显变化。治疗期间,甲组患者出血5例肝损伤,乙组14例肝损伤,乙组患者肝损伤比例明显高于甲组（P<0.05）,乙组患者肝脏损伤发生时间明显晚于甲组（P<0.05）。治疗期间,两组不良反应发生率无统计学差异。结论甲巯咪唑与丙硫氧嘧啶对甲状腺功能亢进的疗效相当。与丙硫氧嘧啶相比,甲巯咪唑对肝脏损伤程度较小,但服药后较早引起肝脏损伤,建议在甲状腺功能亢进治疗期间,应定期复查患者肝功能。     

251例药源性甲状腺功能损害不良反应报告分析

摘 要 目的：探讨引起药源性甲状腺功能损害的药物种类及其不良反应表现特点,为临床合理用药提供依据。方法：收集2010年1月～2017年6月国家药品不良反应监测数据库中浙江省平台上报的不良反应为药源性甲状腺损害的病例,利用Excel 软件统计分析患者性别、年龄、原患疾病、可疑药品种类、不良反应类型、发生时间、临床表现、转归等相关因素。结果：共收集甲状腺损害病例251例252例次。多种药物可引起不同类型的甲状腺功能异常,主要为抗精神病类药物（54.18%）、抗心律失常药物（17.93%）和抗躁狂药物（12.35%）,共占83.46%,其中抗精神病药富马酸喹硫平片发生不良反应例次占总例次的46.83%,绝大多数的不良反应表现为甲状腺功能降低;盐酸胺碘酮片发生不良反应例次占总例次的17.86%,其严重不良反应报告占其ADR报告数的62.22%,不良反应表现为甲状腺功能减退和甲状腺功能亢进,比例约为4.5∶1。碳酸锂片发生不良反应例次占总例次的12.70%,但国内生产的碳酸锂片说明书中不良反应项下均未提及甲状腺功能损害。结论：多种药物可引起药源性甲状腺功能损害,应引起临床应重视,提高用药安全性。     

不同年龄冠心病患者甲状腺功能与冠状动脉病变程度的关系

目的 通过分析不同年龄冠心病（CAD）患者的甲状腺功能[三碘甲状腺原氨酸（TT3）、游离三碘甲状腺原氨酸（FT3）、甲状腺素（TT4）、游离甲状腺素（FT4）、促甲状腺激素（TSH）]与Gensini积分的相关性，探讨甲状腺功能对冠状动脉病变程度的影响。方法 采用回顾队列研究对2016年3月至2017年3月就诊于太和县人民医院确诊为CAD的患者179例进行分析，根据患者年龄分两组（<65岁组和≥65岁组），比较不同年龄组患者TT3、FT3、TT4、FT4、TSH水平的差异；对患者的Gensini积分采用三分位数分为3组（低危组、中危组、高危组），比较不同分组之间的TT3、FT3、TT4、FT4、TSH水平的差异；采用Pearson相关性检验分析甲状腺功能与Gensini积分之间的相关性；对不同年龄组冠脉病变程度影响因素采用有序多分类logistic回归分析。结果 入选患者中有甲状腺功能减退1例（0.559%），亚临床甲状腺功减退12例（6.703%）；不同年龄组之间FT3差异有统计学意义（P<0.05）；不同Gensini积分组之间FT3差异有统计学意义（P<0.05）；Pearson和logistic回归分析发现，≥65岁患者的TT3与Gensini积分呈负相关（r=-0.225，P<0.05），TT3增高是≥65岁患者冠状动脉病变严重程度的保护因素，而<65岁和≥65岁患者FT3和Gensini积分呈负相关，且FT3增高是冠状动脉病变严重程度的保护因素。<65岁患者的TSH和Gensini积分呈正相关（r=0.439，P<0.05），TSH增高是<65岁患者冠状动脉病变严重程度的危险因素。结论 TT3、FT3、TSH对不同年龄段冠心脏病患者的冠状动脉病变程度影响不同，且是影响冠状动脉病变程度的独立因素。     

碳酸锂致甲状腺功能异常16例分析

摘 要 目的：探讨碳酸锂致患者甲状腺功能异常不良反应的特点和影响因素。方法: 收集2015～2017年我院上报的16例碳酸锂致甲状腺功能异常不良反应病例,统计分析患者性别、年龄、原患疾病,碳酸锂用药剂量,发生甲状腺功能异常的潜伏期及临床表现、实验室检查值变化,以及转归等因素。结果: 16例患者中,女性11例,男性5例;原患疾病以双相情感障碍为主,用药至发生甲状腺功能异常的潜伏期为9~424 d。发生药品不良反应时剂量为0.5~1.25 g·d-1,平均剂量为(0.98±0.22)g·d-1。14例（87.5%）患者促甲状腺激素（TSH）有不同程度的升高,8例（50.0%）患者游离甲状腺素（FT4）有不同程度降低,5例（31.25%）患者总甲状腺素 (TT4)有不同程度降低,＞90%的患者游离三碘甲状腺原氨酸（FT3）和总三碘甲状腺原氨酸 (TT3)未报告异常。9例（56.25%）患者经减量、停药及对症治疗后,实验室检查指标均有不同程度的好转。结论: 碳酸锂所致的甲状腺功能异常临床表现以TT4、FT4降低,TSH升高或甲状腺肿大为特征。年龄和性别可能与甲状腺功能异常的发生有关。临床使用碳酸锂时应定期监测甲状腺功能。     

硒酵母片联合甲巯咪唑片治疗自身免疫性甲状腺病伴甲状腺功能亢进患者的疗效观察

目的 观察硒酵母片联合甲巯咪唑片治疗自身免疫性甲状腺病（AITD）伴甲状腺功能亢进患者的疗效,并分析其对血清甲状腺过氧化酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）和促甲状腺素受体抗体（TRAb）水平的影响。方法 以河南科技大学第一附属医院2014年1月至2016年6月收治的80例AITD伴甲状腺功能亢进患者为研究对象,所有患者均经甲状腺超声、甲状腺摄131Ⅰ率和甲状腺核素扫描等检查确诊。按随机数字表法将80例患者分为对照组和观察组,每组各40例。对照组接受甲巯咪唑片治疗,疗程为12个月;观察组在对照组的基础上,增加硒酵母片,疗程为12个月。比较两组患者治疗前后甲状腺激素水平、甲状腺体积和甲状腺抗体水平,并统计治疗总有效率。结果 两组患者治疗后的FT3和FT4水平均较治疗前低（P<0.05）,促甲状腺激素（TSH）水平较治疗前高（P<0.05）;且观察组治疗前后的血清FT3、FT4和TSH水平与对照组比较,差异均有统计学意义（t=2.825、4.084、18.149,P<0.05）。两组治疗后的甲状腺体积数值均较治疗前小（P<0.05）,观察组治疗前后的甲状腺体积差异大于对照组,差异有统计学意义（t=14.511,P<0.001）。两组治疗后的TPOAb、TGAb和TRAb水平均较治疗前低,差异均有统计学意义（P<0.05）;且观察组治疗前后的TPOAb、TGAb和TRAb水平与对照组比较,差异均有统计学意义（t=39.198、71.311、9.839,P<0.001）。观察组患者的治疗有效率高于对照组,差异有统计学意义（χ²=4.781,P=0.029）。结论 硒酵母片联合甲巯咪唑片治疗AITD伴甲状腺功能亢进患者,可有效降低TPOAb、TGAb和TRAb水平,抑制机体甲状腺激素的分泌,改善异常的甲状腺功能,并缩小甲状腺体积,疗效确切,值得在临床上推广应用。     

我国免疫检查点抑制剂致甲状腺相关不良反应文献分析

目的：分析我国免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）致甲状腺相关不良反应（thyroid-immune related adverse events, T-irAEs）的特点及规律,为临床合理用药提供参考。方法：检索中国知网、万方、维普数据自建库至2022年12月关于T-irAEs的文献报道,提取个案数据并进行分析。结果：最终纳入25篇文献,共28例个案报道,患者平均年龄（61.59±10.60）岁,原发疾病为肺癌者最多（64.29%）,T-irAEs发生时间多为用药后3.03个周期,约66.54 d,其中报道的不良反应类型有亚临床甲状腺功能减退3例（10.71%）、甲状腺功能减退13例（46.43%）、甲状腺功能亢进7例（25.00%）及甲状腺炎5例（17.86%）。结论：文献分析显示我国T-irAEs以甲状腺功能减退为多,在ICIs治疗过程中,应加强监测,及时识别,保障患者用药安全。     

终末期肾脏病甲状腺功能异常与甲状腺功能正常患者相关指标比较

目的 比较甲状腺功能异常的终末期肾脏病（ESRD）与甲状腺功能正常的ESRD患者体内的炎症因子、同型半胱氨酸（Hcy）水平差异,并分析研究其体内炎症因子、Hcy与心脏结构的相关性。方法 选择2014年1月至2015年1月合肥市第二人民医院收治的病情稳定的ESRD患者,根据甲状腺功能检测结果,分为亚临床甲状腺功能异常组（42例）与甲状腺功能正常组（53例）,收集患者临床资料和相关生化指标,应用心脏超声测定患者左房内径（LAD）、左室舒张末内径（LVEDd）、左室收缩末内径（LVEDs）、左室后壁厚度（LVPWT）、室间隔厚度（IVST）、左心室质量指数（LVMI）、左室射血分数（LVEF）等,比较分析两组患者的炎症因子水平及心脏结构情况。结果 亚临床甲状腺功能异常组患者LAD、LVEDd、LVEDs、LVPWT、IVST、LVMI高于甲状腺功能正常组,而LVEF低于甲状腺功能正常组,差异有统计学意义（P<0.05）。亚临床甲状腺功能异常组患者hs-CRP、IL-6、Hcy分别与LAD、LVEDd、LVEDs、LVPWT、IVST、LVMI呈正相关,与LVEF呈负相关,差异有统计学意义（P<0.05）。结论 甲状腺功能异常的ESRD患者心脏结构异常发生率高于甲状腺功能正常组,考虑与其体内炎症因子、Hcy水平密切相关。     

131I联合丙硫氧嘧啶治疗对甲亢患者血清CT、PTH、BGP水平及甲状腺功能的影响

摘 要 目的：探讨¹³¹I治联合丙硫氧嘧啶治疗对甲亢患者血清CT、PTH、BGP水平及甲状腺功能的影响。 方法: 甲亢患者80例随机分为观察组和对照组各40例。对照组使用¹³¹I碘治疗,观察组在对照组基础上加用丙硫氧嘧啶。疗程均为2个月。观察两组患者治疗前后血清降钙素（CT）、甲状旁腺素（PTH）、骨钙素（BGP）及甲状腺功能各指标的变化,并记录不良反应。结果: 治疗后,两组血清CT、PTH、BGP,以及甲状腺功能各指标水平均较治疗前得到改善（P<0.05）;且观察组血清CT、BGP,血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）水平均低于对照组,血清PTH、促甲状腺激素（FSH）水平高于对照组（P<0.05）。两组患者药品不良反应发生率比较,差异无统计学意义（P>0.05）。结论:甲亢患者在¹³¹I碘治疗的基础上加用丙硫氧嘧啶可以有效的降低血清CT、BGP的水平,使血清PTH水平增加,促进甲状腺功能得到恢复,值得推广应用。     

小柴胡汤联合泼尼松对肺癌患者免疫性肺炎及T淋巴细胞的影响

目的 探讨小柴胡汤联合泼尼松对肺癌患者免疫性肺炎及T淋巴细胞的影响。方法 将80例免疫检查点抑制剂（ICI）所致免疫性肺炎的肺癌患者随机分为两组,对照组（n=40）采用泼尼松治疗,联合组（n=40）在此基础上加用小柴胡汤。连续治疗7天后,比较两组患者的临床-影像-生理（CRP）评分、T淋巴细胞水平、Karnofsky评分的变化。结果 治疗后,两组CRP评分均显著下降,且联合组显著低于对照组（P<0.05）;治疗后,对照组CD4⁺、CD4⁺/CD8⁺ T细胞亚群水平较治疗前显著下降,且显著低于联合组（P<0.05）;两组治疗后Karnofsky评分均显著升高,且联合组明显高于对照组（P<0.05）。结论 小柴胡汤联合泼尼松治疗肺癌患者免疫性肺炎的疗效优于单用泼尼松,有助于调节免疫抑制状态,增强免疫功能,改善生活质量。     

免疫检查点抑制剂对甲状腺功能影响的研究进展

甲状腺功能紊乱(thyroid dysfunction,TD)是癌症患者在接受免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)治疗过程中最常见的内分泌系统免疫相关不良事件(immune related adverse events,IRAEs)之一。本文主要从免疫治疗相关性甲状腺功能紊乱的发病机制、流行病学、诊疗方面、预后展望进行介绍,使更多内分泌科医师和肿瘤科医师认识、掌握免疫治疗相关甲状腺疾病的临床特点和诊疗策略,加强科间合作,以减轻癌症患者免疫抑制剂治疗过程中遭受的甲状腺不良事件带来的影响。     

Safety evaluation of durvalumab for the treatment of non-small-cell lung cancer

ABSTRACT

Introduction

The development of immune checkpoint inhibitors (ICIs), such as anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, has been a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Durvalumab, a PD-L1 inhibitor, has shown survival benefit as a maintenance therapy for patients with unresectable stage III NSCLC following definitive chemoradiotherapy, and is approved by the U.S. Food and Drug Administration and the European Medicines Agency.     

Oncolytic virotherapy,alone or in combination with immune checkpoint inhibitors,for advanced melanoma: A systematic review and meta-analysis

BackgroundAdvanced melanoma, one of the most lethal forms of skin cancer, remains a difficult condition to treat, despite the substantial scientific progression in cancer treatment. Oncolytic virotherapy (OV), either alone or combined with immune checkpoint inhibitors (ICIs), has often been administrated in an attempt to cure this malignancy. However, the clinical outcomes dramatically vary among different reports.MethodsIn this study, we performed a meta-analysis to evaluate the clinical efficacy and safety profile of OV, combined with ICIs in some cases, in advanced melanoma patients. The original clinical studies were identified based on the online query in PubMed, Cochrane, and Web of Science before December 30, 2018.ResultsA total of 18 publications involving 1472 patients were included for the final meta-analysis. The data concerning objective response rate (ORR) and incidence rate of severe immune-related adverse events (irAEs) were extracted accordingly from the text or supplementary materials. The results illustrated that a single treatment of OV could generate a 25% ORR for advanced melanoma, and the ORR could be improved to 45% if combined with ICIs. Further analysis demonstrated that the introduction of ICIs in OV could increase the incidence rate of severe irAEs (AE ≥ 3) from 12% to 39%. However, the rate attributed to OV remains at 12% in the combination group.ConclusionThe clinical efficacy of OV can be significantly improved by ICIs even though more onerous burden will be exerted simultaneously on the safety profile.     

The safety and efficacy of pembrolizumab for the treatment of non-small cell lung cancer

ABSTRACT

Introduction: Lung cancer is the leading cancer-related cause of death worldwide. The introduction of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has significantly improved the outcome of these patients. Pembrolizumab, a monoclonal IgG4-kappa antibody against programmed-death-1 (PD-1) protein, nowadays represents a standard of care for NSCLC patients. Although it has a favorable toxicity profile, some immune-related adverse events (irAEs) can be life-threatening, therefore its knowledge may help to optimize the care of these patients.

Areas covered: The authors review data regarding the efficacy and safety of pembrolizumab from the most relevant clinical trials as well as toxicities reported in the clinical use. Special considerations of use in special populations will be noted. Finally, its toxicity profile will be compared with other ICIs used in NSCLC.

Expert opinion: In the scenario of NSCLC, pembrolizumab shows a favorable safety profile with less than 10% serious immune-related adverse events (irAEs) when used in monotherapy and without adding relevant extra-toxicity to chemotherapy when used in combination. Monotherapy with pembrolizumab is associated with better health-related quality of life than chemotherapy. Early recognition and appropriate treatment of irAEs is of prime importance as most are reversible if correctly managed. Rechallenge with pembrolizumab is frequently feasible.     

基于聚类分析的免疫检查点抑制剂不良事件文献计量研究

目的 对免疫检查点抑制剂（immune checkpoint inhibitors，ICIs）相关不良事件的研究文献进行计量分析，寻找该领域的研究热点及重点，为后续研究提供参考。方法 检索PubMed、EMbase、CNKI、CBM、VIP及万方数据库，收集相关文献。采用Endnote软件对文献进行筛选；采用Bicomb软件提取数据并分析发表年份、杂志、文献类型等，同时生成高频主题词的词篇矩阵；采用SPSS软件对词篇矩阵进行聚类分析。结果 共纳入文献2 333篇。文献类型最多为论文，语种为英语。发文量前10位的均为外文期刊，其中发文量前3位的杂志分别为《The Lancet Oncology》《Immunotherapy》《Journal of Clinical Oncology》。共获得文献主题词7 091个，经聚类分析，高频主题词可聚为不良事件的具体表现、严重不良事件（肌炎及心肌炎）、常见不良事件（皮肤毒性、肝毒性和内分泌疾病）、不良事件的处理以及ICIs与其他治疗的联合应用等9个大类。结论 该领域自2011年起相关文献发表量快速上升，发表杂志也多为高影响因子期刊。当前的研究热点主要在不良事件的表现形式及发生率、严重不良事件以及常见不良事件的发生机制及其联系、激素在处理不良事件中的应用、ICIs与化疗药物等联合应用时不良事件的发生规律以及ICIs不良事件相关患者的治疗有效性。     

Novel immunotherapy in the treatment of advanced non-small cell lung cancer

Introduction: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed.

Areas covered: The discovery that the immune system plays a fundamental role in the fight against cancer. The cancer cells use mechanisms able to avoid the immune control has led to the development of drugs able to overcome this escape route. The best known checkpoint pathways are the CTLA-4 and PD-1/PD-L1; they suppress T-cell activity in different ways: CTLA-4 regulates T-cell activity at an early stage whereas PD-1 regulates later effector T-cell activity within tissue and tumors. The best characterized checkpoint inhibitors in advanced NSCLC setting are ipilimumab and tremelimumab, (anti-CTLA-4 antibodies), nivolumab and pembrolizumab (anti-PD-1 antibodies), atezolizumab and durvalumab (anti-PD-L1 antibodies). Nivolumab and pembrolizumab have received the FDA and EMA approval for the treatment of NSCLC in second-line setting.

Expert commentary: The role played by tumor microenvironment may be the next area of research to overcome the resistance at the checkpoint inhibitors as well as the identification of biomarkers to better select patients. In addition checkpoint inhibitors are investigate in combination with other agent involved in immune control with promising results in solid tumors.     

PD-1/PD-L1抗体类药物致免疫相关性肾损伤3例的用药分析

程序性细胞死亡受体1(PD-1)和程序性细胞死亡配体1(PD-L1)是免疫检查点抑制剂(ICIs)的主要靶点.为加强药学监护,降低ICIs不良反应的发生率,临床药师对3例肿瘤患者在应用注射用卡瑞利珠单抗、度伐利尤单抗、特瑞普利单抗后出现免疫相关性肾损伤的治疗过程及用药情况进行了研究分析.3个病例经过激素治疗后,肾功能均...     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

Erdafitinib for the treatment of metastatic bladder cancer

ABSTRACT

Introduction: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or metastatic UC (mUC) with FGFR3 or FGFR2 alterations, accounting for 15–20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.

Areas covered: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presented at international conferences were used for the literature search.

Expert opinion: The FDA approval of erdafitinib provided a new treatment option for FGFR-altered UC progressing on platinum-based chemotherapy. It is not clear whether FGFR inhibitor is a preferred second-line treatment choice to ICI. Compared to ICI, erdafitinib has a better response rate in patients with visceral metastases. However, a shorter duration of response and toxicity profile of erdafitinib, particularly ocular toxicity, is an important consideration. Regular eye exams are recommended by the FDA. Tumor profiling during upfront therapy may help identify those who benefit at the time of progression. In summary, a high unmet need remains for new drugs in chemotherapy- and ICI-refractory UC.