PDF(Pubmed)
Abstract：
BACKGROUND: 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).
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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%.
CONCLUSIONS: 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.
摘要：
背景：Nivolumab是欧洲第一个被批准用于治疗晚期肾细胞癌（aRCC）的免疫检查点抑制剂。证人是一个持续的，prospective,旨在评估纳武单抗在法国现实生活(或常规实践)中治疗的aRCC患者中的有效性和安全性的观察性研究(ClinicalTrials.gov标识符:NCT03455452).
方法：本研究包括确诊为aRCC的成年患者，这些患者在1-2次抗血管生成治疗后开始使用纳武单抗。终点包括总生存期(OS)，无进展生存期（PFS），治疗持续时间（DOT），响应持续时间（DOR），总反应率（ORR），亚组分析，和治疗相关不良事件（TRAEs）。这里提供了中位随访12.3个月后的结果。
结果：共纳入325例aRCC患者，其中38.2%的Karnofsky评分<80，77.8%的人接受nivolumab作为二线治疗，69.5%曾接受过肾切除术。在总人口中,中位OS为20.5个月[95%置信区间(CI)17.6~25.0]个月,中位PFS为5.2个月(95%CI4.5~5.9).ORR为34.5%，中位数DOT为3.8个月，中位DOR为16.5个月。Nivolumab在不同的亚组中有效，包括骨或腺转移患者以及接受基线皮质类固醇的患者。此外，无论之前的肾切除术和治疗路线如何,均观察到有效性.没有发现新的安全性信号；32.0%的患者报告了任何等级的TRAE，≥3级和严重TRAE各占11.1%，和TRAEs导致8.9%的停药。
结论：正在进行的WITNESS研究的初步结果证实了纳武单抗单药治疗先前治疗过的aRCC患者的真实世界有效性和安全性。治疗益处与关键III期CheckMate025随机临床试验中观察到的益处相似，尽管范围更广，现实生活中的研究人群。
方法：本研究包括确诊为aRCC的成年患者，这些患者在1-2次抗血管生成治疗后开始使用纳武单抗。终点包括总生存期(OS)，无进展生存期（PFS），治疗持续时间（DOT），响应持续时间（DOR），总反应率（ORR），亚组分析，和治疗相关不良事件（TRAEs）。这里提供了中位随访12.3个月后的结果。
结果：共纳入325例aRCC患者，其中38.2%的Karnofsky评分<80，77.8%的人接受nivolumab作为二线治疗，69.5%曾接受过肾切除术。在总人口中,中位OS为20.5个月[95%置信区间(CI)17.6~25.0]个月,中位PFS为5.2个月(95%CI4.5~5.9).ORR为34.5%，中位数DOT为3.8个月，中位DOR为16.5个月。Nivolumab在不同的亚组中有效，包括骨或腺转移患者以及接受基线皮质类固醇的患者。此外，无论之前的肾切除术和治疗路线如何,均观察到有效性.没有发现新的安全性信号；32.0%的患者报告了任何等级的TRAE，≥3级和严重TRAE各占11.1%，和TRAEs导致8.9%的停药。
结论：正在进行的WITNESS研究的初步结果证实了纳武单抗单药治疗先前治疗过的aRCC患者的真实世界有效性和安全性。治疗益处与关键III期CheckMate025随机临床试验中观察到的益处相似，尽管范围更广，现实生活中的研究人群。
