西米普利单抗治疗晚期皮肤鳞状细胞癌患者的2期开放标签研究（EMPOWER-CSCC-1）：1、2和3组的最终长期分析以及固定剂量治疗组6的初步分析

A phase 2 open-label study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1): Final long-term analysis of groups 1, 2, and 3, and primary analysis of fixed-dose treatment group 6.

作者信息

Hughes Brett G M, Guminski Alexander, Bowyer Samantha, Migden Michael R, Schmults Chrysalyne D, Khushalani Nikhil I, Chang Anne Lynn S, Grob Jean-Jacques, Lewis Karl D, Ansstas George, Day Fiona, Ladwa Rahul, Stein Brian N, Muñoz Couselo Eva, Meier Friedegund, Hauschild Axel, Schadendorf Dirk, Basset-Seguin Nicole, Modi Badri, Dalac-Rat Sophie, Dunn Lara A, Flatz Lukas, Mortier Laurent, Guégan Sarah, Heinzerling Lucie M, Mehnert Janice M, Trabelsi Sabiha, Soria-Rivas Ainara, Stratigos Alexander J, Ulrich Claas, Wong Deborah J, Beylot-Barry Marie, Bossi Paolo, Bugés Sánchez Cristina, Chandra Sunandana, Robert Caroline, Russell Jeffery S, Silk Ann W, Booth Jocelyn, Yoo Suk-Young, Seebach Frank, Lowy Israel, Fury Matthew G, Rischin Danny

机构信息

Department of Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

出版信息

J Am Acad Dermatol. 2025 Jan;92(1):68-77. doi: 10.1016/j.jaad.2024.06.108. Epub 2024 Sep 7.

DOI:10.1016/j.jaad.2024.06.108

PMID:39245360

Abstract

BACKGROUND

In the phase 2 EMPOWER-CSCC-1 study (NCT02760498), cemiplimab demonstrated antitumor activity against metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC).

OBJECTIVES

To report final analysis of weight-based cemiplimab in mCSCC and laCSCC (groups 1 and 2), fixed-dose cemiplimab in mCSCC (group 3), and primary analysis of fixed-dose cemiplimab in mCSCC/laCSCC (group 6).

METHODS

Patients received cemiplimab (3 mg/kg intravenously every 2 weeks [groups 1 and 2]) or cemiplimab (350 mg intravenously [groups 3 and 6]) every 3 weeks. The primary end point was objective response rate (ORR). Duration of response (DOR) and progression-free survival (PFS) are presented per protocol, according to post-hoc sensitivity analyses that only include the period of protocol-mandated imaging assessments.

RESULTS

At 42.5 months, ORR for groups 1-3 (n = 193) was 47.2%, estimated 12-month DOR was 88.3%, and median PFS was 26.0 months. At 8.7 months, ORR for group 6 (n = 165 patients) was 44.8%; median DOR and median PFS were not reached. Serious treatment-emergent adverse event rates (grade ≥3) were groups 1-3: 31.1% and group 6: 34.5%.

LIMITATIONS

Nonrandomized study, nonsurvival primary end point.

CONCLUSION

EMPOWER-CSCC-1 provides the largest prospective data on long-term efficacy and safety for anti-programmed cell death-1 therapy in advanced CSCC.

摘要

背景

在2期EMPOWER-CSCC-1研究（NCT02760498）中，西米普利单抗显示出对转移性皮肤鳞状细胞癌（mCSCC）和局部晚期皮肤鳞状细胞癌（laCSCC）的抗肿瘤活性。

目的

报告mCSCC和laCSCC中基于体重的西米普利单抗（第1组和第2组）、mCSCC中固定剂量西米普利单抗（第3组）以及mCSCC/laCSCC中固定剂量西米普利单抗（第6组）的最终分析结果，以及mCSCC/laCSCC中固定剂量西米普利单抗的初步分析结果。

方法

患者接受西米普利单抗（第1组和第2组每2周静脉注射3mg/kg）或每3周接受西米普利单抗（第3组和第6组静脉注射350mg）。主要终点是客观缓解率（ORR）。缓解持续时间（DOR）和无进展生存期（PFS）根据仅包括方案规定的影像学评估期的事后敏感性分析按方案呈现。

结果

在42.5个月时，第1 - 3组（n = 193）的ORR为47.2%，估计12个月的DOR为88.3%，中位PFS为26.0个月。在8.7个月时，第6组（n = 165例患者）的ORR为44.8%；中位DOR和中位PFS未达到。严重治疗突发不良事件发生率（≥3级）在第1 - 3组为31.1%，在第6组为34.5%。