Zhang Sheng, Ju Mengyang, Wang Qin, Zhu Dongyuan, Liu Zengjun, Ye Xiongjun, Li Wenfeng
Medical Oncology, Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China.
Shanghai University of Engineering Science, Shanghai 201620, China.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyaf202.
Extramammary Paget's disease (EMPD) is a rare cancer without standard therapy. We evaluated the safety and efficacy of a combination of the humanized monoclonal antiprogrammed death-1 (PD-1) antibody, carelizumab, with rivoceranib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in patients with advanced EMPD.
This multicenter, single-arm, phase II trial included 12 patients with EMPD. The primary endpoint is the objective response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. It is hypothesized that the ORR will be less than 10% if the treatment is ineffective and will reach 35% if effective. Secondary endpoints include progression-free survival (PFS) and safety assessments. Eligible patients are aged ≥18 years, with histologically confirmed advanced EMPD. Treatment consists of carelizumab (200 mg intravenously every 3 weeks) and rivoceranib (250 mg orally once daily), with dose adjustments permitted based on toxicity profiles.
Between June 2024 and February 2025, 12 patients were enrolled. One patient withdrew from the trial because of nontreatment-related accidents, and a total of 11 patients completed at least 1 cycle of treatment. The median PFS is 2.4 months (95% CI, 2.1-4.4 months). Among these 11 patients, no patients achieved CR or PR. Six patients (50%) experienced grade 3 adverse events.
This is the first trial evaluating the combination of a PD-1 inhibitor and a VEGFR inhibitor in advanced EMPD. This combination therapy is well tolerated but does not appear to have clinically meaningful activity in advanced EMPD. This trial was registered at the Chinese Clinical Trial number registration: 2400086153.
乳腺外佩吉特病（EMPD）是一种罕见的癌症，尚无标准治疗方法。我们评估了人源化抗程序性死亡-1（PD-1）单克隆抗体卡瑞利珠单抗与血管内皮生长因子受体（VEGFR）抑制剂瑞沃替尼联合应用于晚期EMPD患者的安全性和有效性。
这项多中心、单臂、II期试验纳入了12例EMPD患者。主要终点是客观缓解率（ORR），根据RECIST v1.1标准定义为达到完全缓解（CR）或部分缓解（PR）的患者比例。假设如果治疗无效，ORR将低于10%，如果有效则将达到35%。次要终点包括无进展生存期（PFS）和安全性评估。符合条件的患者年龄≥18岁，经组织学证实为晚期EMPD。治疗方案为卡瑞利珠单抗（每3周静脉注射200mg）和瑞沃替尼（每日口服250mg），并可根据毒性情况调整剂量。
2024年6月至2025年2月期间，共纳入12例患者。1例患者因非治疗相关事故退出试验，共有11例患者完成了至少1个周期的治疗。中位PFS为2.4个月（95%CI，2.1-4.4个月）。在这11例患者中，无患者达到CR或PR。6例患者（50%）发生3级不良事件。
这是第一项评估PD-1抑制剂与VEGFR抑制剂联合应用于晚期EMPD的试验。这种联合治疗耐受性良好，但在晚期EMPD中似乎没有具有临床意义的活性。本试验在中国临床试验注册中心注册，注册号为：2400086153。
