Background:A previous published Phase 2 trial using 2–4 doses of neoadjuvant cemiplimab in stage II–IV resectable cutaneous squamous cell carcinoma (CSCC) demonstrated that a complete pathological (pCR) rate of 51% and major pathological response (mPR) rate of 13% could be achieved with durable disease control.Methods:In this open-label, single-institution phase II trial (NCT05878288), patients with stage II–IV resectable CSCC received up to four doses of neoadjuvant cemiplimab prior to surgery. The primary endpoint of the study was to perform comprehensive molecular profiling. The focus of this report are the secondary clinical endpoints of pCR rate, mPR (defined as <10% viable tumour) rate, overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, immune-modified RECIST (imRECIST) and Immune PET Response Criteria in Solid Tumours (iPERCIST), disease-free survival (DFS), overall survival (OS), safety, and to describe changes in planned surgery.Results:Eleven patients were enrolled, with all proceeding with surgery. An ORR and pCR rate of 73% (8/11; 95% CI 0.39–0.93) was achieved, whilst 3/11 patients progressed on treatment. On pre-operative imaging, all 8/11 pCR patients demonstrated a partial response (RECIST 1.1), whilst 6/8 achieved a complete metabolic response and 2/8 a partial metabolic response (iPERCIST). Median follow-up was 10.2 (IQR 6.7–16.4) months. DFS was 91% (95% CI 0.57–1) and OS was 100% (95% CI 0.68–1), with one non-responder patient who developed recurrent locoregional and distant metastatic disease. There were no unexpected safety signals. Pathological features of response to neoadjuvant immunotherapy most commonly were granulomatous inflammation with keratin, fibrosis and inflammation. No cases with a dense inflammatory infiltrate were observed. Neoadjuvant immunotherapy did not impact the intra-operative planning and execution of surgery, but in the eight pCR cases, it reduced the extent of required surgery, whilst in the three non-responder cases, surgery was more extensive than originally planned.Conclusions:The DISCERN trial confirms that an excellent complete response rate can be achieved with four doses of neoadjuvant immunotherapy in stage II–IV CSCC. Proposed refinements to the pathological assessment of response and metabolic response criteria in CSCC for the neoadjuvant context are provided.
背景：先前一项已发表的II期临床试验显示，对II–IV期可切除皮肤鳞状细胞癌（CSCC）患者使用2–4剂新辅助cemiplimab治疗，可获得51%的完全病理缓解（pCR）率和13%的主要病理缓解（mPR）率，并实现持久的疾病控制。 方法：在这项开放标签、单中心的II期临床试验（NCT05878288）中，II–IV期可切除CSCC患者在手术前接受最多四剂新辅助cemiplimab治疗。研究的主要终点是进行全面的分子特征分析。本报告重点关注的次要临床终点包括：pCR率、mPR率（定义为存活肿瘤细胞<10%）、基于实体瘤疗效评价标准（RECIST）1.1、免疫修饰RECIST（imRECIST）以及实体瘤免疫PET疗效标准（iPERCIST）的总体缓解率（ORR）、无病生存期（DFS）、总生存期（OS）、安全性，以及描述计划手术方案的变化。 结果：共入组11例患者，全部接受了手术。ORR和pCR率达到73%（8/11；95% CI 0.39–0.93），同时有3/11例患者在治疗期间出现疾病进展。在术前影像学评估中，所有8例达到pCR的患者均显示部分缓解（RECIST 1.1），其中6/8例达到完全代谢缓解，2/8例达到部分代谢缓解（iPERCIST）。中位随访时间为10.2个月（IQR 6.7–16.4）。DFS为91%（95% CI 0.57–1），OS为100%（95% CI 0.68–1），仅有一例无应答患者出现局部区域复发和远处转移。未出现非预期的安全性信号。对新辅助免疫治疗产生应答的病理特征最常见的是伴有角蛋白的肉芽肿性炎症、纤维化和炎症。未观察到密集炎性浸润的病例。新辅助免疫治疗未影响手术的术中规划和执行，但在8例达到pCR的病例中，其减少了所需的手术范围；而在3例无应答病例中，手术范围较原计划更为广泛。 结论：DISCERN试验证实，在II–IV期CSCC中，使用四剂新辅助免疫治疗可获得优异的完全缓解率。本研究为CSCC新辅助治疗背景下的病理缓解评估和代谢缓解标准提出了改进建议。
肿瘤(癌症)患者之家