英国皇家马斯登医院Sheela Rao团队研究了Retifanlimab联合卡铂和紫杉醇治疗局部复发或转移性肛管鳞状细胞癌的疗效与安全性。相关论文于2025年6月14日发表在《柳叶刀》杂志上。

Retifanlimab在铂化疗进展的程序性死亡配体1阳性晚期鳞状细胞肛门癌（SCAC）中具有活性。研究组旨在前瞻性地评估在初始卡铂-紫杉醇治疗中加入Retifanlimab治疗这种疾病的益处。

这项全球性、多中心、双盲、随机、对照、三期试验在欧盟、澳大利亚、日本、英国和美国等12个国家的70个中心进行。年龄≥18岁，局部复发或转移性SCAC不能手术，东部肿瘤合作组表现状态为0或1，既往无全身治疗，HIV控制良好（即CD4+计数>200/μL，病毒载量检测不到）的患者符合条件。患者被随机分配（1:1），每4周服用Retifanlimab（静脉注射500毫克）或安慰剂，并联合标准卡铂-紫杉醇治疗长达1年。在确认疾病进展的情况下，安慰剂组患者可以过渡到Retifanlimab单药治疗。主要终点是根据实体肿瘤1.1版应答评价标准独立评估无进展生存期（即从随机化日期到首次记录的进展性疾病或全因死亡的时间）。通过治疗意向来评估疗效。

在2020年11月12日至2023年7月3日期间，376名患者被评估为合格，308名患者被随机分配到Retifanlimab+卡铂-紫杉醇组（n=154）或安慰剂+卡铂-紫杉醇组（n=154）。308例患者中，女性222例（72%），男性86例（28%）。Retifanlimab组的中位无进展生存期为9.3个月（95% CI为7.5 - 11.3），安慰剂组的中位无进展生存期为7.4个月（7.1 - 7.7）。与安慰剂加卡铂-紫杉醇组相比，Retifanlimab加卡铂-紫杉醇组的严重和3级或更严重的不良事件发生率更高（分别为47.4%对38.8%和83.1%对75.0%）。最常见的≥3级不良事件是中性粒细胞减少（Retifanlimab加卡铂-紫杉醇组为35.1%，安慰剂加卡铂-紫杉醇组为29.6%）和贫血（19.5%比20.4%）。Retifanlimab联合卡铂-紫杉醇组发生4例致死性不良事件，其中只有一例（全血细胞减少症）与治疗相关。在安慰剂加卡铂-紫杉醇组中发生了1例致命不良事件，与治疗无关。

研究结果表明，Retifanlimab在晚期肛管鳞状细胞癌的一线化疗中使用时，具有可管理的安全性，可提供临床益处。这些结果提示Retifanlimab联合卡铂+紫杉醇可作为晚期鳞状细胞肛癌患者新的治疗标准。

附：英文原文

Title: Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial

Author: Sheela Rao, Emmanuelle Samalin-Scalzi, Ludovic Evesque, Meher Ben Abdelghani, Federica Morano, Amitesh Roy, Laetitia Dahan, Stefano Tamberi, Amandeep Singh Dhadda, Mark P Saunders, Nathalie Casanova, Rosine Guimbaud, Astrid Lievre, Joan Maurel, Marwan Fakih, Chuan Tian, Jill Harrison, Mark M Jones, Mark Cornfeld, Jean-Philippe Spano, Pauline Rochefort, Sheela Rao, Emmanuelle Samalin-Scalzi, Ludovic Evesque, Meher Ben Abdelghani, Federica Morano, Amitesh Roy, Laetitia Dahan, Stefano Tamberi, Amandeep Singh Dhadda, Mark P Saunders, Nathalie Casanova, Rosine Guimbaud, Astrid Lievre, Joan Maurel, Marwan Fakih, Chuan Tian, Jill Harrison, Mark M Jones, Mark Cornfeld, Jean-Philippe Spano, Pauline Rochefort

Issue&Volume: 2025/06/14

Abstract:

Background

Retifanlimab has activity in programmed death ligand 1-positive advanced squamous cell anal carcinoma (SCAC) that has progressed on platinum chemotherapy. We aimed to prospectively assess the benefit of adding retifanlimab to initial carboplatin–paclitaxel for this disease.

Methods

This global, multicentre, double-blind, randomised, controlled, phase 3 trial was done at 70 centres in 12 countries across the EU, Australia, Japan, the UK, and the USA. Patients aged ≥18 years with inoperable locally recurrent or metastatic SCAC, an Eastern Cooperative Oncology Group performance status of 0 or 1, no previous systemic therapy, and well controlled HIV (ie, CD4+ count >200/μL and undetectable viral load) were eligible. Patients were randomly assigned (1:1) to retifanlimab (500 mg intravenous) or placebo every 4 weeks with standard carboplatin–paclitaxel for up to 1 year. Patients in the placebo group could cross over to retifanlimab monotherapy on confirmed disease progression. The primary endpoint was independently assessed progression-free survival (ie, time from date of randomisation to date of first documented progressive disease or death due to any cause) per Response Evaluation Criteria in Solid Tumours version 1.1. Efficacy was assessed by intention to treat. This trial is registered with ClinicalTrials.gov (NCT04472429) and EUDRA-CT (2020–000826–24) and is active but closed to enrolment.

Findings

Between Nov 12, 2020, and July 3, 2023, 376 patients were assessed for eligibility and 308 were randomly assigned to retifanlimab plus carboplatin–paclitaxel (n=154) or placebo plus carboplatin–paclitaxel (n=154). 222 (72%) of 308 patients were female and 86 (28%) were male. Median progression-free survival was 9·3 months (95% CI 7·5–11·3) in the retifanlimab group and 7·4 months (7·1–7·7) in the placebo group (hazard ratio 0·63 [95% CI 0·47–0·84]; one-sided p=0·0006). Serious and grade 3 or worse adverse events were more frequent in the retifanlimab plus carboplatin–paclitaxel group compared with the placebo plus carboplatin–paclitaxel group (47·4% vs 38·8% and 83·1% vs 75·0%, respectively). The most common grade ≥3 adverse events were neutropenia (35·1% for retifanlimab plus carboplatin–paclitaxel vs 29·6% for placebo plus carboplatin–paclitaxel) and anaemia (19·5% vs 20·4%). Four fatal adverse events occurred in the retifanlimab plus carboplatin–paclitaxel group, only one (pancytopenia) of which was treatment related. One fatal adverse event occurred in the placebo plus carboplatin–paclitaxel group and was not treatment related.

Interpretation

Retifanlimab provides clinical benefit, with a manageable safety profile, when added to first-line chemotherapy in advanced squamous cell carcinoma of the anal canal. These results suggest retifanlimab with carboplatin plus paclitaxel should be considered as the new standard of care for patients with advanced squamous cell anal carcinoma.

DOI: 10.1016/S0140-6736(25)00631-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00631-2/abstract