Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A Phase 2 Study

IF 25.3 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2024-11-01 DOI:10.1016/j.eururo.2024.02.014

Roberto Iacovelli , Chiara Ciccarese , Sebastiano Buti , Paolo Andrea Zucali , Emanuela Fantinel , Davide Bimbatti , Elena Verzoni , Caterina Accettura , Lucia Bonomi , Consuelo Buttigliero , Giuseppe Fornarini , Stefania Pipitone , Francesco Atzori , Cristina Masini , Francesco Massari , Francesca Primi , Alessandro Strusi , Giulia Claire Giudice , Matteo Perrino , Marco Maruzzo , Giampaolo Tortora

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引用次数: 0

Abstract

Background and Objective

Combinations of VEGFR-TKIs plus ICI against PD1/PD-L1 are the standard first-line therapy for patients with mRCC, irrespective of the prognostic class. This study aims to investigate the feasibility and safety of withdrawing the VEGFR-TKI but continuing the anti- PD1/PD-L1 in patients who achieve response to their combination.

Methods

This was a single-arm phase 2 trial in patients with treatment naïve mRCC with prior nephrectomy, without symptomatic/bulky disease and no liver metastases. Enrolled patients received axitinib+avelumab, after 36 weeks of therapy those who achieved tumor response interrupted axitinib and continued avelumab maintenance until disease progression. The primary endpoint was the rate of patients without progression eight weeks after the axitinib interruption. Secondary endpoints were the median value for progression free (mPFS) and overall survival (mOS) and the safety in the overall population.

Key Findings and Limitations

79 patients were enrolled and 75 evaluated for efficacy. A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after eight weeks and thus achieving the primary endpoint. The mPFS of the overall population was 24 months while the mOS was not reached. The ORR was 76% (12% CR, 64% PR), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of AEs of any grade was 59% and 3% for grade 3 or 4. This study was limited by the lack of the comparative arm.

Conclusions and Clinical Implications

The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of response to the VEGFR-TKI+ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance led to decreased side effects and should be further investigated as a new strategy to delay tumor progression.

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阿维单抗加间歇性阿西替尼治疗既往未接受过治疗的转移性肾细胞癌患者。Tide-A 2 期研究。

背景：血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂（TKIs）与抗PD1/PD-L1免疫检查点抑制剂（ICI）的联合疗法是转移性肾细胞癌（mRCC）患者的标准一线疗法，无论预后等级如何：目的：研究在对VEGFR-TKI和PD1/PD-L1联合治疗有反应的患者中，撤消VEGFR-TKI但继续抗PD1/PD-L1的可行性和安全性：这是一项单臂2期试验，对象是既往接受过肾切除术、无症状/大块病变且无肝转移的治疗无效mRCC患者：入组患者接受阿西替尼+阿维单抗治疗；治疗36周后，获得肿瘤应答的患者中断阿西替尼治疗，继续接受阿维单抗维持治疗，直至疾病进展：主要终点是阿西替尼中断治疗8周后无进展的患者比例。次要终点是无进展生存期（mPFS）和总生存期（mOS）的中位值，以及总体人群的安全性：79名患者入组，75名患者接受了疗效评估。根据研究设计，共有29名（38%）患者停用了阿西替尼，其中72%的患者在8周后病情没有进展，因此达到了主要终点。全部患者的 mPFS 为 24 个月，而 mOS 则未达到。客观反应率为76%（12%为完全反应，64%为部分反应），19%的患者病情稳定。在停用阿西替尼的患者中，任何级别的不良反应发生率为：3级59%，4级3%。这项研究因缺乏对比组而受到限制：TIDE-A研究表明，对于有证据表明对一线治疗中使用的VEGFR-TKI+ICI组合有反应的选定mRCC患者，停用VEGFR-TKI并维持ICI治疗是可行的。患者摘要：我们评估了某些接受阿西替尼+阿维列单抗一线联合治疗的晚期肾癌患者在治疗36周后出现肿瘤反应时是否可以中断阿西替尼的治疗。我们发现，中断阿西替尼治疗可提高联合用药的安全性，而维持阿维列单抗治疗则可能延缓肿瘤进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.