目的:卡博替尼和纳武单抗(CaboNivo)单独或与伊匹单抗(CaboNivoIpi)一起在转移性尿路上皮癌(mUC)患者中显示出良好的疗效和安全性,转移性肾细胞癌(mRCC),和罕见的泌尿生殖系统(GU)肿瘤在剂量递增I期研究中。我们报告安全性的最终数据分析,总反应率(ORR),无进展生存期(PFS),I期患者和7个扩展队列的总生存期(OS)。
方法:这是研究者发起的,多中心,第一阶段审判。CaboNivo双峰扩展队列包括(1)MUC,(2)mRCC,和(3)膀胱/脐尿管腺癌;CaboNivoIpi三联体扩增队列包括(1)mUC,(2)mRCC,(3)阴茎癌,和(4)膀胱鳞状细胞癌和其他罕见的GU肿瘤(ClinicalTrials.gov标识符:NCT02496208)。
结果:该研究纳入了120例接受CaboNivo(n=64)或CaboNivoIpi(n=56)治疗的患者,中位随访时间为49.2个月。在108名可评估患者中(CaboNivon=59;CaboNivoIpin=49),ORR为38%(完全缓解率11%),中位缓解持续时间为20个月.MUC的ORR为42.4%,mRCC为62.5%(n=16),膀胱鳞状细胞癌占85.7%(n=7),44.4%为阴茎癌(n=9),肾髓样癌占50.0%(n=2)。84%的CaboNivo患者和80%的CaboNivoIpi患者发生≥3级治疗相关不良事件。
结论:CaboNivo和CaboNivoIpi在患有多种GU恶性肿瘤的患者中具有临床活性和安全性,特别是透明细胞RCC,尿路上皮癌,和罕见的GU肿瘤,如膀胱鳞状细胞癌,膀胱小细胞癌,膀胱腺癌,肾髓样癌,还有阴茎癌.
OBJECTIVE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.
METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).
RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.
CONCLUSIONS: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.