Dana-Farber Cancer Institute, Boston, Massachusetts.
The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2021 Mar 15;127(6):840-849. doi: 10.1002/cncr.33328. Epub 2020 Nov 20.
In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616).
Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1).
Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related.
Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing.
Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination.
在这项多中心、单臂、多队列、2 期试验中，评估了纳武利尤单抗和伊匹单抗在晚期罕见泌尿生殖系统癌症患者中的疗效，包括膀胱和上尿路上皮癌（BUTCVH）、肾上腺肿瘤、铂类难治性生殖细胞肿瘤、阴茎癌和前列腺癌（NCT03333616）。
纳入了无既往免疫检查点抑制剂暴露的罕见泌尿生殖系统恶性肿瘤患者。患者每 3 周接受 3 mg/kg 的纳武利尤单抗和 1 mg/kg 的伊匹单抗静脉输注 4 剂，然后每 4 周静脉输注 480 mg 的纳武利尤单抗。主要终点是根据实体瘤反应评价标准（版本 1.1）评估的客观缓解率（ORR）。
在 2018 年 4 月至 2019 年 7 月期间，在 6 个机构共纳入了 55 名患者，分为 3 个队列：BUTCVH（n=19）、肾上腺肿瘤（n=18）和其他肿瘤（n=18）。中位随访时间为 9.9 个月（范围，1-21 个月）。28 名患者（51%）接受了 4 剂纳武利尤单抗和伊匹单抗；25 名患者接受了纳武利尤单抗维持治疗，中位治疗周期为 4 个周期（范围，1-18 个周期）。总的研究 ORR 为 16%（95%置信区间，10%-25%）；BUTCVH 队列的 ORR 为 37%，包括 2 例完全缓解，其他 2 个队列的 ORR 为 6%。22 名患者（40%）发生了与治疗相关的 3 级或更高毒性反应；24%（n=13）需要高剂量类固醇（≥40mg 泼尼松或等效物）。3 名患者发生了 5 级事件；1 例死亡与治疗相关。
纳武利尤单抗和伊匹单抗在罕见泌尿生殖系统恶性肿瘤患者的亚组中产生了客观缓解，尤其是那些 BUTCVH 患者。目前正在进行另一项队列研究，以更好地确定神经内分泌分化的泌尿生殖系统肿瘤对该方案的活性。
患有罕见癌症的患者通常被排除在研究之外，并且治疗选择有限。55 名罕见泌尿生殖系统肿瘤患者从多个地点入组并接受纳武利尤单抗和伊匹单抗治疗，这一方案用于治疗肾癌。该方案在一些患者中显示出活性，特别是那些患有膀胱或上尿路上皮癌的患者，这些患者的组织学不常见或存在变异；其中 37%的患者对治疗有反应。目前正在进行更多的研究，以更好地确定哪些患者最受益于这种联合治疗。
