高危皮肤鳞状细胞癌辅助使用西米普利单抗或安慰剂

Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma.

作者信息

Rischin Danny, Porceddu Sandro, Day Fiona, Brungs Daniel P, Christie Hayden, Jackson James E, Stein Brian N, Su Yungpo Bernard, Ladwa Rahul, Adams Gerard, Bowyer Samantha E, Otty Zulfiquer, Yamazaki Naoya, Bossi Paolo, Challapalli Amarnath, Hauschild Axel, Lim Annette M, Patel Vishal A, Walker Joanna L, De Liz Vassen Schurmann Maite, Queirolo Paola, Cañueto Javier, Ferreira da Silva Flavio Augusto, Stratigos Alexander, Guminski Alexander, Lin Charles, Damian Fernanda, Flatz Lukas, Taylor Anne E, Carr David R, Harris Samuel, Kirtbaya Dmitry, Quereux Gaëlle, Rutkowski Piotr, Basset-Seguin Nicole, Khushalani Nikhil I, Robert Caroline, Ju Haisong, Joseph Camryn, Bansal Shikha, Chen Chieh-I, Seebach Frank, Yoo Suk-Young, Lowy Israel, Goncalves Priscila, Fury Matthew G

机构信息

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

出版信息

N Engl J Med. 2025 May 31. doi: 10.1056/NEJMoa2502449.

DOI:10.1056/NEJMoa2502449

PMID:40454639

Abstract

BACKGROUND

Patients who have cutaneous squamous-cell carcinoma with high-risk features are at risk for recurrence after definitive local therapy. The benefit of systemic adjuvant therapy options has not been well established in clinical trials.

METHODS

In a phase 3, randomized trial, we enrolled patients with local or regional cutaneous squamous-cell carcinoma, after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature). Patients were assigned in a 1:1 ratio to receive adjuvant cemiplimab (350 mg) or placebo, administered intravenously every 3 weeks for 12 weeks, followed by a dose increase to 700 mg administered every 6 weeks for up to 36 weeks (≤48 weeks total). The primary end point was disease-free survival. Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, and safety.

RESULTS

A total of 415 patients were assigned to cemiplimab (209) or placebo (206). The median follow-up was 24 months. Cemiplimab was superior to placebo with respect to disease-free survival (24 vs. 65 events; hazard ratio for disease recurrence or death, 0.32; 95% confidence interval [CI], 0.20 to 0.51; P<0.001). The estimated 24-month disease-free survival was 87.1% (95% CI, 80.3 to 91.6) with cemiplimab and 64.1% (95% CI, 55.9 to 71.1) with placebo. Cemiplimab led to lower risks of locoregional recurrence (9 events, vs. 40 with placebo; hazard ratio, 0.20; 9% CI, 0.09 to 0.40) and distant recurrence (10 vs. 26 events; hazard ratio, 0.35; 95% CI, 0.17 to 0.72). Adverse events of grade 3 or higher occurred in 23.9% of the patients who received cemiplimab and in 14.2% of those who received placebo; discontinuation due to adverse events occurred in 9.8% and 1.5%, respectively.

CONCLUSIONS

Adjuvant cemiplimab therapy led to longer disease-free survival than placebo among patients at high risk for recurrence of cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; C-POST ClinicalTrials.gov number, NCT03969004.).

摘要

背景

具有高危特征的皮肤鳞状细胞癌患者在接受确定性局部治疗后有复发风险。系统性辅助治疗方案的益处尚未在临床试验中得到充分证实。

方法

在一项3期随机试验中，我们纳入了局部或区域皮肤鳞状细胞癌患者，这些患者在手术切除和术后放疗后，由于淋巴结特征（最大直径≥20mm的淋巴结包膜外扩展或至少三个受累淋巴结）或非淋巴结特征（皮下转移、T4病变[伴有骨侵犯]、神经周围侵犯或局部复发肿瘤且伴有≥1个其他风险特征）而具有高复发风险。患者按1:1比例分配接受辅助性西米普利单抗（350mg）或安慰剂治疗，每3周静脉注射一次，共12周，随后剂量增加至700mg，每6周注射一次，最长36周（总疗程≤48周）。主要终点是无病生存期。次要终点包括局部区域无复发生存期、远处无复发生存期和安全性。

结果

共有415例患者被分配接受西米普利单抗治疗（209例）或安慰剂治疗（206例）。中位随访时间为24个月。在无病生存期方面，西米普利单抗优于安慰剂（分别为24例和65例事件；疾病复发或死亡的风险比为0.32；95%置信区间[CI]为0.20至0.51；P<0.001）。接受西米普利单抗治疗的患者估计24个月无病生存率为87.1%（95%CI为80.3至91.6），接受安慰剂治疗的患者为64.1%（95%CI为55.9至71.1）。西米普利单抗降低了局部区域复发风险（9例事件，安慰剂组为40例；风险比为0.20；9%CI为0.09至0.40）和远处复发风险（10例事件，安慰剂组为26例；风险比为0.35；95%CI为0.17至0.72）。接受西米普利单抗治疗的患者中3级或更高等级的不良事件发生率为23.9%，接受安慰剂治疗的患者为14.2%；因不良事件停药的发生率分别为9.8%和1.5%。