Xavier García Del Muro, David Páez López-Bravo, Miler Andrés Cuéllar-Rivas, Pablo Maroto, Patrizia Giannatempo, Daniel Castellano, Miguel A Climent, Begoña P Valderrama, Alfonso Gómez de Liaño, Laura López-Montero, Leonardo Mina, Daniel Alcalá-López, Miguel Sampayo-Cordero, Andrea Necchi
{"title":"雷替凡利单抗治疗晚期阴茎鳞状细胞癌:ORPHEUS 2 期研究","authors":"Xavier García Del Muro, David Páez López-Bravo, Miler Andrés Cuéllar-Rivas, Pablo Maroto, Patrizia Giannatempo, Daniel Castellano, Miguel A Climent, Begoña P Valderrama, Alfonso Gómez de Liaño, Laura López-Montero, Leonardo Mina, Daniel Alcalá-López, Miguel Sampayo-Cordero, Andrea Necchi","doi":"10.1016/j.euo.2024.04.021","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>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.</p><p><strong>Patient summary: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Retifanlimab in Advanced Penile Squamous Cell Carcinoma: The Phase 2 ORPHEUS Study.\",\"authors\":\"Xavier García Del Muro, David Páez López-Bravo, Miler Andrés Cuéllar-Rivas, Pablo Maroto, Patrizia Giannatempo, Daniel Castellano, Miguel A Climent, Begoña P Valderrama, Alfonso Gómez de Liaño, Laura López-Montero, Leonardo Mina, Daniel Alcalá-López, Miguel Sampayo-Cordero, Andrea Necchi\",\"doi\":\"10.1016/j.euo.2024.04.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>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.</p><p><strong>Patient summary: </strong>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.</p>\",\"PeriodicalId\":12256,\"journal\":{\"name\":\"European urology oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2024-05-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European urology oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.euo.2024.04.021\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European urology oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.euo.2024.04.021","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景和目的:晚期阴茎鳞状细胞癌(PSCC)患者的预后较差,可供选择的治疗方案非常有限。大多数阴茎鳞状细胞癌病例的PD-L1表达较高,这与预后较差有关。针对PD-L1的免疫疗法可使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:ORPHEUS是一项单臂、多中心、2期试验,18名晚期/转移性PSCC患者既往未接受过抗PD-1/抗PD-L1药物治疗。根据实体瘤反应评估标准 v1.1,主要终点是客观反应率(ORR)。次要终点包括临床获益率(CBR)、疾病控制率、反应持续时间(DoR)、反应时间、无进展生存期(PFS)、总生存期(OS)、最大肿瘤缩小率和安全性。主要终点采用 Wilson 方法,次要终点采用 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);3名患者出现部分反应。中位DoR为3.3个月(范围1.8-8.5)。CBR 为 22.2% (95% CI 6.4-47.6%)。中位 PFS 为 2.0 个月(95% CI 1.6-3.3),中位 OS 为 7.2 个月(95% CI 3.0-9.8)。一名患者(5.6%)出现了3级治疗相关不良事件(AE)。没有 >= 4 级的治疗相关不良事件。样本量小是主要的局限性:单药瑞替单抗在晚期/转移性PSCC中显示出临床活性信号,没有新的安全性信号。患者总结:晚期鳞状细胞型阴茎癌是一种罕见的肿瘤,预后较差。这种癌症的侵袭性通常与高水平的PD-L1蛋白有关。我们研究了针对PD-1的免疫疗法药物retifanlimab是否对这种类型的阴茎癌具有活性。三分之一的患者肿瘤消退或稳定,副作用可控。
Retifanlimab in Advanced Penile Squamous Cell Carcinoma: The Phase 2 ORPHEUS Study.
Background and 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.
Key findings and limitations: 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 and clinical implications: 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.
Patient summary: 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.
期刊介绍:
Journal Name: European Urology Oncology
Affiliation: Official Journal of the European Association of Urology
Focus:
First official publication of the EAU fully devoted to the study of genitourinary malignancies
Aims to deliver high-quality research
Content:
Includes original articles, opinion piece editorials, and invited reviews
Covers clinical, basic, and translational research
Publication Frequency: Six times a year in electronic format