Barthélémy P, Albigès L, Escudier B, Narciso B, Bigot P, Chehimi M, Emambux S, Calcagno F, Mouillet G, Eymard J-C, Schlürmann F, Bailly S, Garbay D, Berdah J-F, Palmaro M B, Goupil M G, Spaeth D, Néré S, Quentric C, Vano Y-A, Thiery-Vuillemin A
Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg.
Department of Medical Oncology, Gustave Roussy Cancer Campus, Paris.
ESMO Open. 2024 Jul;9(7):103602. doi: 10.1016/j.esmoop.2024.103602. Epub 2024 Jun 18.
Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452).
This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here.
A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%.
Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.
纳武利尤单抗是欧洲首个获批用于治疗对先前抗血管生成治疗耐药的晚期肾细胞癌（aRCC）患者的免疫检查点抑制剂。WITNESS是一项正在进行的前瞻性观察性研究，旨在评估纳武利尤单抗在法国现实生活（或常规实践）中接受治疗的aRCC患者中的有效性和安全性（ClinicalTrials.gov标识符：NCT03455452）。
本研究纳入确诊为aRCC且在接受1 - 2线先前抗血管生成治疗后开始使用纳武利尤单抗的成年患者。终点包括总生存期（OS）、无进展生存期（PFS）、治疗持续时间（DOT）、缓解持续时间（DOR）、总缓解率（ORR）、亚组分析以及治疗相关不良事件（TRAEs）。本文展示了中位随访12.3个月后的结果。
共纳入325例aRCC患者，其中38.2%的患者卡诺夫斯基评分<80，77.8%的患者接受纳武利尤单抗作为二线治疗，69.5%的患者曾接受过肾切除术。在总体人群中，中位OS为20.5 [95%置信区间（CI）17.6 - 25.0]个月，中位PFS为5.2（95% CI 4.5 - 5.9）个月。ORR为34.5%，中位DOT为3.8个月，中位DOR为16.5个月。纳武利尤单抗在不同亚组中均有效，包括有骨或腺体转移的患者以及接受基线皮质类固醇治疗的患者。此外，无论先前是否进行肾切除术及治疗线数如何，均观察到有效性。未发现新的安全信号；32.0%的患者报告了任何级别的TRAEs，≥3级和严重TRAEs各占11.1%，因TRAEs导致停药的占8.9%。
正在进行的WITNESS研究的初步结果证实了纳武利尤单抗单药治疗在先前接受治疗的aRCC患者中的现实世界有效性和安全性。尽管研究人群更广泛且来自现实生活，但治疗获益与关键的III期CheckMate 025随机临床试验中观察到的相似。
