Abstract：
OBJECTIVE: Patients with advanced penile squamous cell carcinoma (PSCC) have poor outcomes and very limited therapeutic options are available. Most PSCC cases have high PD-L1 expression, which is associated with worse prognosis. Immunotherapy targeting PD-L1 could benefit patients with PSCC. Our aim was to evaluate the efficacy and safety of the anti-PD-1 antibody retifanlimab in patients with advanced/metastatic PSCC.
METHODS: ORPHEUS was a single-arm, multicenter, phase 2 trial in 18 patients with advanced/metastatic PSCC, previously untreated with anti-PD-1/anti-PD-L1 agents. Patients received retifanlimab 500 mg intravenously every 4 wk for up to 2 yr. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included the clinical benefit rate (CBR), disease control rate, duration of response (DoR), time to response, progression-free survival (PFS), overall survival (OS), maximum tumor shrinkage, and safety. The Wilson method was used for the primary endpoint, and the Clopper-Pearson and Kaplan-Meier methods for secondary endpoints.
UNASSIGNED: Median follow-up was 7.2 mo. The ORR was 16.7% (95% confidence interval [CI] 5.8-39.2); three patients had a partial response. Median DoR was 3.3 mo (range 1.8-8.5). The CBR was 22.2% (95% CI 6.4-47.6%). Median PFS was 2.0 mo (95% CI 1.6-3.3) and median OS was 7.2 mo (95% CI 3.0-9.8). One patient (5.6%) experienced grade 3 treatment-related adverse events (AEs). There were no grade >= 4 treatment-related AEs. The small sample size is the main limitation.
CONCLUSIONS: Single-agent retifanlimab exhibited signals of clinical activity in advanced/metastatic PSCC, with no new safety signals. Further investigation of retifanlimab in this setting is warranted.
RESULTS: Advanced penile cancer of the squamous cell type is a rare tumor with poor prognosis. The aggressiveness of this cancer is usually associated with high levels of a protein called PD-L1. We investigated whether retifanlimab, an immunotherapy drug against PD-1, has activity against this type of penile cancer. Tumor regression or stabilization occurred in one-third of the patients and the side effects were manageable.
METHODS: ORPHEUS was a single-arm, multicenter, phase 2 trial in 18 patients with advanced/metastatic PSCC, previously untreated with anti-PD-1/anti-PD-L1 agents. Patients received retifanlimab 500 mg intravenously every 4 wk for up to 2 yr. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included the clinical benefit rate (CBR), disease control rate, duration of response (DoR), time to response, progression-free survival (PFS), overall survival (OS), maximum tumor shrinkage, and safety. The Wilson method was used for the primary endpoint, and the Clopper-Pearson and Kaplan-Meier methods for secondary endpoints.
UNASSIGNED: Median follow-up was 7.2 mo. The ORR was 16.7% (95% confidence interval [CI] 5.8-39.2); three patients had a partial response. Median DoR was 3.3 mo (range 1.8-8.5). The CBR was 22.2% (95% CI 6.4-47.6%). Median PFS was 2.0 mo (95% CI 1.6-3.3) and median OS was 7.2 mo (95% CI 3.0-9.8). One patient (5.6%) experienced grade 3 treatment-related adverse events (AEs). There were no grade >= 4 treatment-related AEs. The small sample size is the main limitation.
CONCLUSIONS: Single-agent retifanlimab exhibited signals of clinical activity in advanced/metastatic PSCC, with no new safety signals. Further investigation of retifanlimab in this setting is warranted.
RESULTS: Advanced penile cancer of the squamous cell type is a rare tumor with poor prognosis. The aggressiveness of this cancer is usually associated with high levels of a protein called PD-L1. We investigated whether retifanlimab, an immunotherapy drug against PD-1, has activity against this type of penile cancer. Tumor regression or stabilization occurred in one-third of the patients and the side effects were manageable.
摘要：
目的：晚期阴茎鳞状细胞癌（PSCC）患者的预后较差，可获得的治疗选择非常有限。大多数PSCC病例具有高PD-L1表达，这与预后较差有关。针对PD-L1的免疫治疗可以使PSCC患者受益。我们的目的是评估抗PD-1抗体retifanlimab在晚期/转移性PSCC患者中的疗效和安全性。
方法：ORPHEUS是单臂，多中心，在18例晚期/转移性PSCC患者中进行的2期试验，以前未经抗PD-1/抗PD-L1药物治疗。患者每4周静脉注射retifanlimab500mg，持续2年。主要终点是根据实体瘤v1.1的反应评估标准的客观反应率（ORR）。次要终点包括临床获益率（CBR），疾病控制率,响应持续时间(DoR)，响应时间,无进展生存期（PFS），总生存期（OS），最大肿瘤收缩，和安全。威尔逊方法用于主要终点，以及次要终点的Clopper-Pearson和Kaplan-Meier方法。
■中位随访时间为7.2个月。ORR为16.7％（95％置信区间[CI]5.8-39.2）；三名患者有部分反应。平均DoR为3.3mo（范围1.8-8.5）。CBR为22.2%（95%CI6.4-47.6%）。中位PFS为2.0mo（95%CI1.6-3.3），中位OS为7.2mo（95%CI3.0-9.8）。1例患者（5.6%）出现3级治疗相关不良事件（AE）。没有>=4级治疗相关的AE。小样本量是主要限制。
结论：单药retifanlimab在晚期/转移性PSCC中表现出临床活性信号，没有新的安全信号.在这种情况下，有必要对retifanlimab进行进一步的研究。
结果：鳞状细胞型晚期阴茎癌是一种罕见的肿瘤，预后不良。这种癌症的侵袭性通常与高水平的称为PD-L1的蛋白质有关。我们调查了retifanlimab，一种针对PD-1的免疫治疗药物，对这种类型的阴茎癌具有活性。三分之一的患者发生肿瘤消退或稳定，副作用可控。
方法：ORPHEUS是单臂，多中心，在18例晚期/转移性PSCC患者中进行的2期试验，以前未经抗PD-1/抗PD-L1药物治疗。患者每4周静脉注射retifanlimab500mg，持续2年。主要终点是根据实体瘤v1.1的反应评估标准的客观反应率（ORR）。次要终点包括临床获益率（CBR），疾病控制率,响应持续时间(DoR)，响应时间,无进展生存期（PFS），总生存期（OS），最大肿瘤收缩，和安全。威尔逊方法用于主要终点，以及次要终点的Clopper-Pearson和Kaplan-Meier方法。
■中位随访时间为7.2个月。ORR为16.7％（95％置信区间[CI]5.8-39.2）；三名患者有部分反应。平均DoR为3.3mo（范围1.8-8.5）。CBR为22.2%（95%CI6.4-47.6%）。中位PFS为2.0mo（95%CI1.6-3.3），中位OS为7.2mo（95%CI3.0-9.8）。1例患者（5.6%）出现3级治疗相关不良事件（AE）。没有>=4级治疗相关的AE。小样本量是主要限制。
结论：单药retifanlimab在晚期/转移性PSCC中表现出临床活性信号，没有新的安全信号.在这种情况下，有必要对retifanlimab进行进一步的研究。
结果：鳞状细胞型晚期阴茎癌是一种罕见的肿瘤，预后不良。这种癌症的侵袭性通常与高水平的称为PD-L1的蛋白质有关。我们调查了retifanlimab，一种针对PD-1的免疫治疗药物，对这种类型的阴茎癌具有活性。三分之一的患者发生肿瘤消退或稳定，副作用可控。
