Abstract：
OBJECTIVE: To describe the molecular profile of a real-world cohort of patients with metastatic urothelial carcinoma (mUC) and to evaluate the benefit of next-generation sequencing (NGS) panels in guiding therapy in patients with mUC and the outcomes of DNA-matched treatments recommended by a multidisciplinary molecular tumor board (MMTB).
METHODS: This was a single-center analysis of a real-world cohort of adult patients with mUC included in an ongoing trial that aimed to evaluate the clinical utility of NGS for solid tumors. Genomic analysis was performed for each patient, most of them using the Ion Torrent Oncomine Focus Assay. Genomic results were discussed during MMTB meetings.
RESULTS: We included 43 patients with mUC treated with platinum-based combinations and immunotherapy. Twenty-five patients (58.1%; 95% CI 43.4-72.9) had at least one tumor pathogenic alteration. The MMTB classified 16 (48.5%) of the 33 tumor pathogenic alterations found in our real-world cohort of mUC patients as ESCAT I, which is the maximum grade of actionability. After excluding patients who were not candidates for targeted therapies, the MMTB provided guidance on matched therapy for seven patients. Among these patients, three achieved a partial response for an overall response rate of 42.9%, a median progression-free survival of 7.3 months (95% CI 6.7-7.9) and a median overall survival of 10.9 months (95% CI 2.4-19.5).
CONCLUSIONS: We recommend that all patients with mUC undergo NGS at diagnosis given the high percentage of patients with pathogenic alterations in our real-world cohort and the efficacy data of patients treated with targeted therapies.
METHODS: This was a single-center analysis of a real-world cohort of adult patients with mUC included in an ongoing trial that aimed to evaluate the clinical utility of NGS for solid tumors. Genomic analysis was performed for each patient, most of them using the Ion Torrent Oncomine Focus Assay. Genomic results were discussed during MMTB meetings.
RESULTS: We included 43 patients with mUC treated with platinum-based combinations and immunotherapy. Twenty-five patients (58.1%; 95% CI 43.4-72.9) had at least one tumor pathogenic alteration. The MMTB classified 16 (48.5%) of the 33 tumor pathogenic alterations found in our real-world cohort of mUC patients as ESCAT I, which is the maximum grade of actionability. After excluding patients who were not candidates for targeted therapies, the MMTB provided guidance on matched therapy for seven patients. Among these patients, three achieved a partial response for an overall response rate of 42.9%, a median progression-free survival of 7.3 months (95% CI 6.7-7.9) and a median overall survival of 10.9 months (95% CI 2.4-19.5).
CONCLUSIONS: We recommend that all patients with mUC undergo NGS at diagnosis given the high percentage of patients with pathogenic alterations in our real-world cohort and the efficacy data of patients treated with targeted therapies.
摘要：
目的：描述转移性尿路上皮癌（mUC）患者的真实世界队列的分子谱，并评估下一代测序（NGS）小组在指导mUC患者治疗方面的益处以及多学科分子肿瘤委员会（MMTB）推荐的DNA匹配治疗的结果。
方法：这是对正在进行的试验中纳入的mUC成年患者的真实队列的单中心分析，该试验旨在评估NGS在实体瘤中的临床应用。对每位患者进行基因组分析，他们中的大多数使用离子激流Oncomine焦点分析。在MMTB会议期间讨论了基因组结果。
结果：我们纳入了43例接受铂类联合治疗和免疫治疗的mUC患者。25例患者（58.1％；95％CI43.4-72.9）至少有一种肿瘤致病性改变。MMTB将在我们真实世界的mUC患者队列中发现的33种肿瘤致病性改变中的16种（48.5％）分类为ESCATI，这是行动能力的最大等级。在排除不适合靶向治疗的患者后，MMTB为7例患者提供了匹配治疗指导.在这些患者中,三人获得部分缓解，总缓解率为42.9%，中位无进展生存期为7.3个月(95%CI6.7~7.9),中位总生存期为10.9个月(95%CI2.4~19.5).
结论：我们建议所有mUC患者在诊断时接受NGS治疗，因为在我们的真实世界队列中，有致病性改变的患者比例很高，并且有靶向治疗的患者的疗效数据。
方法：这是对正在进行的试验中纳入的mUC成年患者的真实队列的单中心分析，该试验旨在评估NGS在实体瘤中的临床应用。对每位患者进行基因组分析，他们中的大多数使用离子激流Oncomine焦点分析。在MMTB会议期间讨论了基因组结果。
结果：我们纳入了43例接受铂类联合治疗和免疫治疗的mUC患者。25例患者（58.1％；95％CI43.4-72.9）至少有一种肿瘤致病性改变。MMTB将在我们真实世界的mUC患者队列中发现的33种肿瘤致病性改变中的16种（48.5％）分类为ESCATI，这是行动能力的最大等级。在排除不适合靶向治疗的患者后，MMTB为7例患者提供了匹配治疗指导.在这些患者中,三人获得部分缓解，总缓解率为42.9%，中位无进展生存期为7.3个月(95%CI6.7~7.9),中位总生存期为10.9个月(95%CI2.4~19.5).
结论：我们建议所有mUC患者在诊断时接受NGS治疗，因为在我们的真实世界队列中，有致病性改变的患者比例很高，并且有靶向治疗的患者的疗效数据。
