Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal.
Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal.
Adv Ther. 2023 Oct;40(10):4134-4150. doi: 10.1007/s12325-023-02624-9. Epub 2023 Aug 22.
This work provides a summary of guideline recommendations and an expert position on the use of maintenance avelumab therapy based on a review of current international clinical practice guidelines for locally advanced or metastatic urothelial carcinoma (UC). A PubMed literature search was conducted in March 2022 (updated in July 2023) to identify guidelines for locally advanced or metastatic UC. An expert panel (four oncologists and one urologist) reviewed the guidelines and clinical evidence, and discussed practical questions regarding the use of avelumab maintenance therapy in this clinical setting. The National Comprehensive Cancer Network, European Association of Urology and European Society for Medical Oncology guidelines recommend first-line cisplatin-containing chemotherapy for cisplatin-eligible patients, carboplatin-gemcitabine for cisplatin-ineligible patients who are fit for carboplatin, or immunotherapy with programmed death ligand-1 (PD-L1) inhibitors (e.g. atezolizumab) in platinum-ineligible patients. Maintenance avelumab is recommended in patients with response/stable disease following chemotherapy (regardless of PD-L1 status). In patients who relapse after/during chemotherapy, options include immunotherapy, erdafitinib [in those with fibroblast growth factor receptor (FGFR) mutations], enfortumab vedotin or further chemotherapy. The expert panel provided the following practical guidance: (1) consider maintenance avelumab in all eligible patients; (2) continue avelumab until disease progression/unacceptable toxicity; (3) ideally, administer six cycles of platinum-based chemotherapy prior to maintenance avelumab; (4) perform radiological evaluation after four chemotherapy cycles and prior to maintenance avelumab; (5) carboplatin-gemcitabine followed by maintenance avelumab is preferred in cisplatin-ineligible patients (regardless of PD-L1 expression), but consider first-line immunotherapy in PD-L1-positive patients and platinum-ineligible patients (regardless of PD-L1 status); and (6) for patients who relapse on avelumab, second-line options include enfortumab vedotin, FGFR inhibitors (in those with FGFR mutations) or clinical trial inclusion. In conclusion, avelumab maintenance therapy is recommended following platinum-based chemotherapy in all eligible patients with locally advanced or metastatic UC, continued until disease progression or unacceptable toxicity.
这篇工作提供了基于对局部晚期或转移性尿路上皮癌（UC）的当前国际临床实践指南的审查，关于使用维持avelumab 治疗的指南建议和专家立场的总结。2022 年 3 月（2023 年 7 月更新）进行了 PubMed 文献检索，以确定局部晚期或转移性 UC 的指南。一个专家小组（四位肿瘤学家和一位泌尿科医生）审查了指南和临床证据，并讨论了在这种临床情况下使用avelumab 维持治疗的实际问题。国家综合癌症网络、欧洲泌尿外科学会和欧洲肿瘤内科学会指南建议顺铂治疗适合的患者进行含顺铂的一线化疗，适合顺铂的卡铂-吉西他滨治疗不耐受顺铂的患者，或无铂治疗适合的患者进行程序性死亡配体-1（PD-L1）抑制剂（例如阿替利珠单抗）免疫治疗。在化疗后有反应/疾病稳定的患者中推荐使用维持avelumab（无论 PD-L1 状态如何）。在化疗后/期间复发的患者中，选择包括免疫治疗、厄达替尼（有纤维母细胞生长因子受体（FGFR）突变的患者）、恩福妥单抗维迪特或进一步化疗。专家组提供了以下实用指导：（1）考虑在所有符合条件的患者中使用维持avelumab；（2）在疾病进展/无法接受的毒性之前继续使用avelumab；（3）理想情况下，在使用avelumab 维持治疗之前先进行六周期的铂类化疗；（4）在四个化疗周期后和使用avelumab 维持治疗之前进行影像学评估；（5）卡铂-吉西他滨联合avelumab 是不耐受顺铂的患者（无论 PD-L1 表达如何）的首选，但考虑 PD-L1 阳性患者和无铂治疗适合的患者（无论 PD-L1 状态如何）的一线免疫治疗；（6）对于在avelumab 治疗中复发的患者，二线选择包括恩福妥单抗维迪特、FGFR 抑制剂（有 FGFR 突变的患者）或临床试验纳入。总之，在所有局部晚期或转移性 UC 的符合条件的患者中，在基于铂类的化疗后推荐使用avelumab 维持治疗，持续至疾病进展或无法耐受的毒性。
