特泊替尼联合阿昔替尼对比舒尼替尼作为晚期肾细胞癌一线治疗：一项随机、开放标签、III 期 RENOTORCH 研究。

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing.

Department of Urology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha.

出版信息

Ann Oncol. 2024 Feb;35(2):190-199. doi: 10.1016/j.annonc.2023.09.3108. Epub 2023 Oct 21.

DOI:10.1016/j.annonc.2023.09.3108

PMID:37872020

Abstract

BACKGROUND

Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC.

PATIENTS AND METHODS

Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety.

RESULTS

A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group.

CONCLUSION

In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

摘要

背景

免疫检查点抑制剂联合酪氨酸激酶抑制剂是晚期透明细胞肾细胞癌（RCC）的标准治疗方法。这项 III 期 RENOTORCH 研究比较了 toripalimab 联合 axitinib 与舒尼替尼作为中/高危晚期 RCC 一线治疗的疗效和安全性。

患者和方法

将中/高危不可切除或转移性 RCC 患者按 1:1 的比例随机分配，接受 toripalimab（240mg 静脉注射，每 3 周一次）联合 axitinib（5mg 口服，每日两次）或舒尼替尼[50mg 口服，每 4 周一次（6 周周期）或 2 周一次（3 周周期）]。主要终点是独立评审委员会（IRC）评估的无进展生存期（PFS）。次要终点是研究者评估的 PFS、总缓解率（ORR）、总生存期（OS）和安全性。

结果

共 421 例患者被随机分配接受 toripalimab 联合 axitinib（n=210）或舒尼替尼（n=211）治疗。IRC 评估的中位随访 14.6 个月，与舒尼替尼相比，toripalimab 联合 axitinib 显著降低了疾病进展或死亡风险 35%[风险比（HR）0.65，95%置信区间（CI）0.49-0.86；P=0.0028]。toripalimab-axitinib 组的中位 PFS 为 18.0 个月，而舒尼替尼组为 9.8 个月。IRC 评估的 ORR 在 toripalimab-axitinib 组明显高于舒尼替尼组（56.7%比 30.8%；P<0.0001）。也观察到 toripalimab 联合 axitinib 组 OS 有获益趋势（HR 0.61，95%CI 0.40-0.92）。toripalimab-axitinib 组 61.5%的患者和舒尼替尼组 58.6%的患者发生治疗相关 3 级及以上不良事件。