PDF(Pubmed)
Abstract：
Platinum-based chemotherapy has been the cornerstone of first-line treatment for advanced urothelial carcinoma for decades, based on its proven efficacy and well-characterized safety profile. Although enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy versus platinum-based chemotherapy in the EV-302 phase 3 trial, common and potentially cumulative toxicities associated with EV plus pembrolizumab may make this combination less suitable for some patients, such as those with pre-existing neuropathy, hyperglycemia, or hepatic impairment, or patients likely to have favorable outcomes with platinum-based chemotherapy. The availability of EV plus pembrolizumab in various countries may also be limited by financial considerations. Thus, platinum-based chemotherapy is likely to remain a valuable option for advanced urothelial carcinoma. Eligibility for cisplatin- or carboplatin-based regimens can be determined by assessing renal function, performance status, and specific comorbidities. In cisplatin-eligible and -ineligible patients without disease progression following platinum-based chemotherapy, avelumab first-line maintenance is standard of care based on findings from the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab first-line maintenance plus best supportive care prolonged overall survival and progression-free survival compared with best supportive care alone across clinically relevant subgroups. Adverse events associated with avelumab were generally consistent with those observed with other immune checkpoint inhibitors, and long-term follow-up showed no new safety concerns with prolonged treatment. Efficacy benefits and safety profiles were similar in patients who received avelumab first-line maintenance after cisplatin- or carboplatin-based chemotherapy. The effectiveness and safety of avelumab first-line maintenance have been confirmed in several real-world studies. Overall, these data support the use of avelumab first-line maintenance for all platinum-treated patients without disease progression. In this podcast, we discuss the evolving role of platinum-based chemotherapy in this disease setting in the context of EV-302 trial results and describe practical considerations in patients receiving first-line cisplatin- or carboplatin-based chemotherapy followed by avelumab maintenance therapy.
摘要：
几十年来，以铂为基础的化疗一直是晚期尿路上皮癌一线治疗的基石，基于其已证明的疗效和良好的安全性。尽管enfortumabvedotin（EV）联合pembrolizumab在EV-3023期试验中显示出优于铂类化疗的疗效，与EV+pembrolizumab相关的常见和潜在累积毒性可能使这种组合不太适合某些患者，比如那些预先存在神经病变的人，高血糖症,或肝功能损害，或患者可能有良好的结果与铂类药物为基础的化疗。EV+pembrolizumab在不同国家的可用性也可能受到财务考虑的限制。因此，铂类化疗可能仍然是晚期尿路上皮癌的一个有价值的选择.以顺铂或卡铂为基础的方案的资格可以通过评估肾功能来确定，性能状态，和特定的合并症。在铂类化疗后无疾病进展的顺铂患者中，基于JAVELIN膀胱1003期试验的结果，阿维鲁单抗一线维持是标准的治疗方法，这表明,在临床相关亚组中,与单用最佳支持治疗相比,阿维鲁单抗一线维持治疗加最佳支持治疗延长了总生存期和无进展生存期.与avelumab相关的不良事件通常与其他免疫检查点抑制剂观察到的不良事件一致。长期随访显示,长期治疗没有新的安全性问题.在基于顺铂或卡铂的化疗后接受阿维鲁单抗一线维持治疗的患者中，疗效获益和安全性相似。阿维鲁单抗一线维持的有效性和安全性已经在一些现实世界的研究中得到证实。总的来说,这些数据支持对所有接受铂类治疗且无疾病进展的患者使用阿维鲁单抗一线治疗.在这个播客中，我们在EV-302试验结果的背景下讨论了铂类化疗在这一疾病背景下的演变作用,并描述了在接受基于顺铂或卡铂的一线化疗后接受阿维鲁单抗维持治疗的患者中的实际考虑因素.
