García Del Muro Xavier, Páez López-Bravo David, Cuéllar-Rivas Miler Andrés, Maroto Pablo, Giannatempo Patrizia, Castellano Daniel, Climent Miguel A, P Valderrama Begoña, Gómez de Liaño Alfonso, López-Montero Laura, Mina Leonardo, Alcalá-López Daniel, Sampayo-Cordero Miguel, Necchi Andrea
Medical Oncology Department, Catalan Institute of Oncology, IDIBELL, University of Barcelona, Barcelona, Spain.
Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Eur Urol Oncol. 2025 Apr;8(2):278-286. doi: 10.1016/j.euo.2024.04.021. Epub 2024 May 15.
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.
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.
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.
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.
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.
晚期阴茎鳞状细胞癌（PSCC）患者预后较差，可用的治疗选择非常有限。大多数PSCC病例的程序性死亡配体1（PD-L1）表达较高，这与较差的预后相关。针对PD-L1的免疫疗法可能使PSCC患者获益。我们的目的是评估抗程序性死亡蛋白1（PD-1）抗体瑞替凡利单抗在晚期/转移性PSCC患者中的疗效和安全性。
ORPHEUS是一项单臂、多中心的2期试验，入组了18例晚期/转移性PSCC患者，这些患者既往未接受过抗PD-1/抗PD-L1药物治疗。患者每4周静脉注射500mg瑞替凡利单抗，持续2年。主要终点是根据实体瘤疗效评价标准第1.1版确定的客观缓解率（ORR）。次要终点包括临床获益率（CBR）、疾病控制率、缓解持续时间（DoR）、起效时间、无进展生存期（PFS）、总生存期（OS）、最大肿瘤缩小程度和安全性。主要终点采用威尔逊方法分析，次要终点采用克洛普-皮尔逊方法和卡普兰-迈耶方法分析。
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）；3例患者出现部分缓解。中位DoR为3.3个月（范围1.8-8.5）。CBR为22.2%（95%CI6.4-47.6%）。中位PFS为2.0个月（95%CI1.6-3.3），中位OS为7.2个月（95%CI3.0-9.8）。1例患者（5.6%）发生3级治疗相关不良事件（AE）。无≥4级治疗相关AE。样本量小是主要局限性。
单药瑞替凡利单抗在晚期/转移性PSCC中显示出临床活性信号，且无新的安全信号。有必要进一步研究瑞替凡利单抗在该情况下的应用。
晚期鳞状细胞型阴茎癌是一种预后较差的罕见肿瘤。这种癌症的侵袭性通常与一种名为PD-L1的蛋白质水平升高有关。我们研究了抗PD-1免疫治疗药物瑞替凡利单抗对这种类型阴茎癌是否有活性。三分之一的患者出现肿瘤消退或稳定，且副作用可控。
