Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial.

IF 10.3 1区医学 Q1 IMMUNOLOGY

Journal for Immunotherapy of Cancer Pub Date : 2025-05-24 DOI:10.1136/jitc-2025-012045

Jérémy Blanc, Aurélien Carnot, Philippe Barthélémy, Vinciane Casert, Brieuc Sautois, Jan Van den Brande, Vincent Vanhaudenarde, Lionel Staudacher, Emmanuel Seront, Veronique Debien, Lieveke Ameye, Nuria Kotecki, Françoise Rothé, Sandrine Rorive, Jean-Christophe Fantoni, Thibault Tricard, Thierry Roumeguère, Ahmad Awada, Nieves Martinez Chanza

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引用次数: 0

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Trial registration number: NCT03674424.

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基于avelumab的肌肉浸润性膀胱癌患者新辅助治疗（AURA Oncodistinct-004）：一项2期多中心临床试验

背景：免疫治疗正在成为非转移性肌肉浸润性膀胱癌（MIBC）的标准治疗方法。化疗-免疫联合治疗的最佳化疗伙伴尚不清楚。我们评估了以阿维鲁单抗为基础的新辅助治疗方案在MIBC患者中的有效性和安全性。方法：多中心2期AURA试验（NCT03674424）招募了接受根治性膀胱切除术的非转移性MIBC患者。符合顺铂条件的患者随机接受avelumab和剂量密集的甲氨蝶呤-长春碱-阿霉素-顺铂（ddmvaca）或吉西他滨-顺铂（GC-A）。不适合顺铂治疗的患者接受单抗(A)或联合紫杉醇-吉西他滨（PG-A）治疗。主要终点为病理完全缓解（pCR）。次要终点包括安全性、无事件生存期和总生存期（OS）。结果：在2018年7月至2021年9月期间，137名符合条件的患者入组了试验。在符合顺铂条件的队列中（n=79）， ddmvaca组的pCR率为58% (95% CI: 42%至72%)，GC-A组的pCR率为53% （95% CI: 37%至68%）。ddmvaca的36个月OS率为87% (95% CI: 76% - 98%)， GC-A为67% （95% CI: 53% - 84%）。在顺铂不合格队列（n=58）中，PG-A组的pCR率为14% (95% CI: 6%至31%)，A组的pCR率为32% （95% CI: 18%至51%）。PG-A的36个月OS率为48% (95% CI: 33%至71%)，a为42% （95% CI: 27%至65%）。总体而言，51例（38%）患者经历了3-4级治疗相关不良事件。结论：Avelumab联合以顺铂为基础的新辅助化疗在MIBC中显示出良好的疗效和良好的安全性，ddMVAC方案也是如此。在不适合顺铂治疗的患者中，avelumab单药治疗显示出令人鼓舞的活性，PG-A方案没有观察到额外的益处。这些结果支持在未来的3期试验中，ddMVAC方案作为新辅助化疗-免疫治疗联合的潜在化疗伙伴，为目前正在研究的GC方案提供了一种替代方案。试验注册号：NCT03674424。

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来源期刊

Journal for Immunotherapy of Cancer Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

17.70

自引率

4.60%

发文量

522

审稿时长

18 weeks

期刊介绍： The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.