阿维鲁单抗联合吉西他滨用于晚期平滑肌肉瘤二线治疗的二期临床试验（EAGLES，韩国癌症研究组UN18-09）

Phase 2 trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (EAGLES, Korean Cancer Study Group UN18-09)

CANCER

影响因子:5.1

分区:医学1区 Top / 肿瘤学2区

发表日期:2025 Jan 01

作者: Miso Kim, Yu Jung Kim, Koung Jin Suh, Se Hyun Kim, Jeong Eun Kim, Juhyeon Jeong, Jung Yong Hong, Jeeyun Lee, Su Jin Lee, Sung Yong Oh, Jung Hoon Kim, Gyeong-Won Lee, Mi Sun Ahn, Wonyoung Choi, Yoon Ji Choi, Taebum Lee, Chiyoon Oum, Jeongkyu Kim, Young Saing Kim, Jin-Hee Ahn

DOI: 10.1002/cncr.35609

摘要

在这项单臂、多中心的二期临床试验中，作者评估了阿维鲁单抗联合吉西他滨在一线化疗失败的平滑肌肉瘤（LMS）患者中的疗效和安全性。晚期LMS患者接受阿维鲁单抗10 mg/kg，在第1天和第15天给药（最长24个月）以及吉西他滨1000 mg/m²，在28天周期的第1、8和15天给药，直至疾病进展或耐受性毒性无法忍受。主要终点为客观反应率（ORR）。共入组38名患者，其中35名可评估，ORR为20%（95%置信区间；[CI]，8%-37%）。疾病控制率为71%，缓解持续时间中位数为21.8个月（范围7.6至≥43.3个月）。无进展生存期中位数为5.6个月（95% CI，4.5-6.8个月），总生存期中位数为27.5个月（95% CI，20.4-34.6个月）。3-4级不良事件发生在70%的患者中，最常见的是粒细胞减少（54%）。免疫介导的不良事件发生在5名患者（14%；甲状腺功能减退，n=3；肝炎，n=2）。肿瘤浸润淋巴细胞密度较高（高于中位数）患者显示更佳的ORR（35%对8%；p=0.104）、无进展生存期（中位数7.3对3.3个月；p=0.024）以及总生存期（中位数尚未达到对21.5个月；p=0.027）。阿维鲁单抗联合吉西他滨显示出在一线治疗失败的晚期LMS患者中具有良好的疗效和安全性。肿瘤浸润淋巴细胞密度可能是预测免疫治疗联合化疗反应的重要因素。

Abstract

In this single-arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first-line chemotherapy.Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR).In total, 38 patients were enrolled. Of these, 35 patients were evaluable, and the ORR was 20% (95% confidence interval; [CI], 8%-37%). The disease control rate was 71%, and the median duration of response was 21.8 months (range, 7.6 to ≥43.3 months). The median progression free-survival was 5.6 months (95% CI, 4.5-6.8 months), and the median overall survival was 27.5 months (95% CI, 20.4-34.6 months). Grade 3-4 adverse events occurred in 70% of patients, of which neutropenia was the most common (54%). Immune-mediated adverse events occurred in five patients (14%; hypothyroidism, n = 3; hepatitis, n = 2). Patients who had a higher density of tumor-infiltrating lymphocytes (greater than the median) exhibited better ORR (35% vs. 8%; p = .104), progression-free survival (median, 7.3 vs. 3.3 months; p = .024), and overall survival (median, not reached vs. 21.5 months; p = .027).The combination of avelumab and gemcitabine demonstrated promising efficacy and manageable safety in patients with advanced LMS who progressed on first-line therapy. Tumor-infiltrating lymphocyte density may be an important factor in predicting the response to combining immunotherapy with chemotherapy.