纳武利尤单抗联合伊匹木单抗对比舒尼替尼用于晚期肾细胞癌的一线治疗：III 期 CheckMate 214 试验疗效和安全性的 8 年扩展随访结果。
Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety from the phase III CheckMate 214 trial.
机构信息
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Medical Oncology (Département de Médecine Oncologique), Gustave Roussy, Villejuif, France.
出版信息
Ann Oncol. 2024 Nov;35(11):1026-1038. doi: 10.1016/j.annonc.2024.07.727. Epub 2024 Aug 2.
BACKGROUND
Nivolumab plus ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years of median follow-up from CheckMate 214.
PATIENTS AND METHODS
Patients with aRCC (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. The endpoints included OS, independent radiology review committee (IRRC)-assessed progression-free survival (PFS), and IRRC-assessed objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients.
RESULTS
With 8 years (99.1 months) of median follow-up, the hazard ratio [HR; 95% confidence interval (CI)] for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). The median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1 months-not estimable (NE) versus 19.8-33.2 months] in ITT patients, 82.8 versus 19.8 months (54.1 months-NE versus 16.4-26.4 months) in I/P patients, and 61.5 versus 33.2 months (27.8 months-NE versus 24.8-51.4 months) in FAV patients. The incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time.
CONCLUSIONS
Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.
背景
纳武利尤单抗联合伊匹木单抗（NIVO+IPI）在晚期肾细胞癌（aRCC）患者中显示出优于舒尼替尼（SUN）的总生存期（OS）和持久缓解获益，并具有长期随访。我们报告了 CheckMate 214 最长 8 年中位随访的更新分析结果。
方法
患者随机分为 NIVO 3 mg/kg 联合 IPI 1 mg/kg Q3W×4 剂量，随后接受 NIVO（3 mg/kg 或 240 mg Q2W 或 480 mg Q4W）；或 SUN（50 mg）每日一次，持续 4 周，停药 2 周。终点包括 OS、独立影像学审查委员会（IRRC）评估的无进展生存期（PFS）和 IRRC 评估的客观缓解率（ORR）在中/高危（I/P；主要）、意向治疗（ITT；次要）和有利风险（FAV；探索性）患者中。
结果
在 8 年（99.1 个月）的中位随访中，NIVO+IPI 与 SUN 相比，ITT 患者的 OS 风险比（HR；95%置信区间[CI]）为 0.72（0.62-0.83），I/P 患者为 0.69（0.59-0.81），FAV 患者为 0.82（0.60-1.13）。90 个月时的 PFS 概率分别为 22.8%比 10.8%（ITT）、25.4%比 8.5%（I/P）和 12.7%比 17.0%（FAV）。与 SUN 相比，NIVO+IPI 的 ORR 为 39.5%比 33.0%（ITT）、42.4%比 27.5%（I/P）和 29.6%比 51.6%（FAV）。在所有国际转移性肾细胞癌数据库联盟（IMDC）风险组中，NIVO+IPI 比 SUN 有更高的完全缓解率（ITT，12.0%比 3.5%；I/P，11.8%比 2.6%；FAV，12.8%比 6.5%）。与 SUN 相比，NIVO+IPI 的中位缓解持续时间（95%CI）为 76.2 比 25.1 个月[ITT 患者 59.1 个月-NE 比 19.8-33.2 个月；I/P 患者 82.8 个月-NE 比 16.4-26.4 个月；FAV 患者 61.5 个月-NE 比 27.8 个月-比 24.8-51.4 个月]。治疗相关不良事件的发生率与先前的报告一致。对 FAV 患者、根据其反应状态、临床亚组和随时间推移的不良事件接受后续治疗的患者进行了探索性事后分析。
结论
NIVO+IPI 与 SUN 相比，在 8 年的时间里，在晚期肾细胞癌患者中显示出优越的生存、持久的缓解获益和可管理的安全性，这是一线检查点抑制剂联合治疗最长的 III 期随访。
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