Abstract：
OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC).
METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval.
RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively.
CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).
METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval.
RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively.
CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).
摘要：
目的：报告尿病，尿液分析变化，无病生存率（DFS），参加膀胱内卡介苗芽孢杆菌(BCG)联合全身派姆珠单抗治疗复发性或持续性高级别非肌层浸润性膀胱癌(HGNMIBC)的I期剂量递增试验(NCT02324582)的受试者的2年和总生存期(OS).
方法：18名患者同意这项研究。五是屏幕故障。使用膀胱镜检查和细胞学检查并对可疑病变进行活检来确定临床活动。在治疗前评估尿液分析和国际前列腺症状评分，第10周（在BCG和pembrolizumab联合治疗期间），治疗完成后3个月和6个月。使用混合模型重复测量分析来分析IPSS。使用卡方检验比较每个间隔的尿液分析结果。
结果：经尿道电切术后与治疗前的病理分期为pTa6（46.2％），CIS为6（46.2%），和pT1在1（7.7%）。在整个治疗过程中，报告的排尿烦恼没有增加。生活质量测量表明主观负担没有变化。在尿液分析中，与基线评估相比,我们在3个月时没有观察到显著差异.12个月时,DFS和OS分别为69.23%和92.31%，分别。24个月时,DFS和OS分别为38.46%和92.31%，分别。
结论：卡介苗与静脉内pembrolizumab联合治疗未显示增加的排尿障碍或不良的尿分析变化。两年的反应数据是有希望的，正在等待III期研究的确认（Keynote676）。
方法：18名患者同意这项研究。五是屏幕故障。使用膀胱镜检查和细胞学检查并对可疑病变进行活检来确定临床活动。在治疗前评估尿液分析和国际前列腺症状评分，第10周（在BCG和pembrolizumab联合治疗期间），治疗完成后3个月和6个月。使用混合模型重复测量分析来分析IPSS。使用卡方检验比较每个间隔的尿液分析结果。
结果：经尿道电切术后与治疗前的病理分期为pTa6（46.2％），CIS为6（46.2%），和pT1在1（7.7%）。在整个治疗过程中，报告的排尿烦恼没有增加。生活质量测量表明主观负担没有变化。在尿液分析中，与基线评估相比,我们在3个月时没有观察到显著差异.12个月时,DFS和OS分别为69.23%和92.31%，分别。24个月时,DFS和OS分别为38.46%和92.31%，分别。
结论：卡介苗与静脉内pembrolizumab联合治疗未显示增加的排尿障碍或不良的尿分析变化。两年的反应数据是有希望的，正在等待III期研究的确认（Keynote676）。
