AVELUMAB与晚期平滑肌肉瘤中吉西他滨联合使用的第二阶段试验作为二线治疗（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)
影响因子:5.10000
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
摘要
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循环直到他们发展出疾病进展或无法忍受的毒性。主要终点是客观反应率（ORR）。总共招募了38名患者。其中，可以评估35例患者，ORR为20％（95％的置信区间； [CI]，8％-37％）。疾病控制率为71％，中位反应持续时间为21.8个月（范围为7.6至≥43.3个月）。中位游离生存期为5.6个月（95％CI，4.5-6.8个月），中位总生存期为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，其中中性粒细胞减少症是最常见的（54％）。免疫介导的不良事件发生在五名患者中（14％；甲状腺功能减退症，n = 3；肝炎，n = 2）。具有更高密度的肿瘤淋巴细胞密度（大于中位数）表现出更好的ORR（35％vs. 8％； P = .104），无进展生存期（中位数，7.3 vs. 3.3个月vs. 3.3个月； P = .024; P = .024），总生存率和总生存率（未达到21..5个月; P = .027）。在一线治疗方面进步的晚期LMS患者的有希望的功效和可管理的安全性。肿瘤淋巴细胞密度可能是预测对免疫疗法与化学疗法相结合的反应的重要因素。
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.