University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
University of Colorado Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Cancer Res Commun. 2023 Jun 8;3(6):1004-1012. doi: 10.1158/2767-9764.CRC-23-0060. eCollection 2023 Jun.
Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC.
Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0-1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9-78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5-99.9). Median DoR was 8.3 months (interquartile range, 4.6-15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25-14.63) and median OS was 30.81 months (95% CI, 24.2-not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib.
Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations.
ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822.
This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months.
免疫检查点抑制剂和 VEGFR 抑制剂联合治疗转移性肾细胞癌（mRCC）患者具有显著疗效。本 I/II 期临床试验评估了 pembrolizumab 和 cabozantinib 联合治疗 mRCC 患者的安全性和疗效。
符合条件的患者患有透明细胞或非透明细胞组织学的 mRCC，具有足够的器官功能，东部合作肿瘤学组（ECOG）体能状态 0-1，且既往未接受过 pembrolizumab 或 cabozantinib 治疗。主要终点是推荐的 II 期剂量（RP2D）的客观缓解率（ORR）。次要终点包括安全性、疾病控制率（DCR）、缓解持续时间（DoR）、无进展生存期（PFS）和总生存期（OS）。
共纳入 45 例患者。共 40 例患者接受了 pembrolizumab 200 mg 静脉注射，每 3 周一次，以及 cabozantinib 60 mg 口服，每日一次的 RP2D 治疗，其中 38 例可评估疗效。所有可评估患者的 ORR 为 65.8%（95%CI，49.9-78.8）[一线治疗为 78.6%，二线治疗为 58.3%]。DCR 为 97.4%（95%CI，86.5-99.9）。DoR 的中位数为 8.3 个月（四分位距，4.6-15.1）。在中位随访 23.54 个月时，中位 PFS 为 10.45 个月（95%CI，6.25-14.63），中位 OS 为 30.81 个月（95%CI，24.2-未达到）。最常见的 1 级和/或 2 级治疗相关不良事件（TRAE）为腹泻、厌食、味觉障碍、体重减轻和恶心。最常见的 3 级和/4 级 TRAE 为高血压、低磷血症、丙氨酸转氨酶升高、腹泻和疲劳。有 1 例与 cabozantinib 相关的可逆性后部脑病综合征（RESP）的 5 级 TRAE。
在 mRCC 患者中，pembrolizumab 和 cabozantinib 联合治疗显示出令人鼓舞的初步疗效和可管理的毒性特征，与其他可用的检查点抑制剂-酪氨酸激酶抑制剂联合治疗相当。
美国国立卫生研究院临床试验注册处：NCT03149822（https://clinicaltrials.gov/ct2/show/NCT03149822）。
本研究评估了 pembrolizumab 和 cabozantinib 联合治疗 mRCC 患者的安全性和有效性。该方案具有可管理的安全性。该联合方案显示出令人鼓舞的活性，客观缓解率为 65.8%，中位 PFS 为 10.45 个月，中位 OS 为 30.81 个月。
