Blanc Jérémy, Carnot Aurélien, Barthélémy Philippe, Casert Vinciane, Sautois Brieuc, Van den Brande Jan, Vanhaudenarde Vincent, Staudacher Lionel, Seront Emmanuel, Debien Veronique, Ameye Lieveke, Kotecki Nuria, Rothé Françoise, Rorive Sandrine, Fantoni Jean-Christophe, Tricard Thibault, Roumeguère Thierry, Awada Ahmad, Martinez Chanza Nieves
Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
Medical Oncology Department, Centre Oscar Lambret, Lille, France.
J Immunother Cancer. 2025 May 24;13(5):e012045. doi: 10.1136/jitc-2025-012045.
Immunotherapy is becoming a standard of care for non-metastatic muscle-invasive bladder cancer (MIBC). The optimal chemotherapy partner for chemo-immunotherapy combinations remains unknown. We evaluated the efficacy and safety of neoadjuvant avelumab-based regimens in patients with MIBC.
The multicenter phase 2 AURA trial (NCT03674424) enrolled patients with non-metastatic MIBC undergoing radical cystectomy. Cisplatin-eligible patients were randomized to receive avelumab with either dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC-A) or gemcitabine-cisplatin (GC-A). Cisplatin-ineligible patients received either avelumab alone (A) or combined with paclitaxel-gemcitabine (PG-A). The primary endpoint was pathological complete response (pCR). Secondary endpoints included safety, event-free survival, and overall survival (OS).
Between July 2018 and September 2021, 137 eligible patients were enrolled in the trial. In the cisplatin-eligible cohort (n=79), pCR rates were 58% (95% CI: 42% to 72%) in the ddMVAC-A arm and 53% (95% CI: 37% to 68%) in the GC-A arm. The 36-month OS rates were 87% (95% CI: 76% to 98%) for ddMVAC-A and 67% (95% CI: 53% to 84%) for GC-A. In the cisplatin-ineligible cohort (n=58), pCR rates were 14% (95% CI: 6% to 31%) in the PG-A arm and 32% (95% CI: 18% to 51%) in the A arm. The 36-month OS rates were 48% (95% CI: 33% to 71%) for PG-A and 42% (95% CI: 27% to 65%) for A. Overall, 51 (38%) patients experienced grade 3-4 treatment-related adverse events.
Avelumab combined with cisplatin-based neoadjuvant chemotherapy showed promising efficacy in MIBC with a favorable safety profile, also with the ddMVAC regimen. Among cisplatin-ineligible patients, avelumab monotherapy showed encouraging activity, with no additional benefit observed from the PG-A regimen. These results support the use of the ddMVAC regimen as a potential chemotherapy partner for neoadjuvant chemo-immunotherapy combinations in future phase 3 trials, providing an alternative to the GC regimen currently under investigation.
NCT03674424.
免疫疗法正成为非转移性肌肉浸润性膀胱癌（MIBC）的标准治疗方法。化疗免疫疗法联合方案中最佳的化疗搭档尚不清楚。我们评估了基于阿维鲁单抗的新辅助治疗方案在MIBC患者中的疗效和安全性。
多中心2期AURA试验（NCT03674424）纳入了接受根治性膀胱切除术的非转移性MIBC患者。符合顺铂治疗条件的患者被随机分配接受阿维鲁单抗联合剂量密集型甲氨蝶呤-长春花碱-阿霉素-顺铂（ddMVAC-A）或吉西他滨-顺铂（GC-A）。不符合顺铂治疗条件的患者单独接受阿维鲁单抗（A）或联合紫杉醇-吉西他滨（PG-A）。主要终点是病理完全缓解（pCR）。次要终点包括安全性、无事件生存期和总生存期（OS）。
2018年7月至2021年9月期间，137名符合条件的患者入组该试验。在符合顺铂治疗条件的队列（n = 79）中，ddMVAC-A组的pCR率为58%（95%CI：42%至72%），GC-A组为53%（95%CI：37%至68%）。ddMVAC-A组的36个月OS率为87%（95%CI：76%至98%），GC-A组为67%（95%CI：53%至84%）。在不符合顺铂治疗条件的队列（n = 58）中，PG-A组的pCR率为14%（95%CI：6%至31%），A组为32%（95%CI：18%至51%）。PG-A组的36个月OS率为48%（95%CI：33%至71%），A组为42%（95%CI：27%至65%）。总体而言，51名（38%）患者发生3-4级治疗相关不良事件。
阿维鲁单抗联合基于顺铂的新辅助化疗在MIBC中显示出有前景的疗效，安全性良好，ddMVAC方案亦是如此。在不符合顺铂治疗条件的患者中，阿维鲁单抗单药治疗显示出令人鼓舞的活性，PG-A方案未观察到额外获益。这些结果支持在未来的3期试验中使用ddMVAC方案作为新辅助化疗免疫疗法联合方案的潜在化疗搭档，为目前正在研究的GC方案提供了一种替代方案。
NCT03674424。
Zotero 插件