在这项单臂、多中心、2 期试验中，作者评估了 avelumab 联合吉西他滨对一线化疗失败的平滑肌肉瘤 (LMS) 患者的疗效和安全性。晚期 LMS 患者每天接受 10 mg/kg avelumab 治疗1 和 15（最多 24 个月）在 28 天周期的第 1、8 和 15 天加用吉西他滨 1000 mg/m2，直到出现疾病进展或无法耐受的毒性。主要终点是客观缓解率 (ORR)。总共 38 名患者入组。其中，35 名患者可评估，ORR 为 20%（95% 置信区间；[CI]，8%-37%）。疾病控制率为71%，中位缓解持续时间为21.8个月（范围7.6至≥43.3个月）。中位无进展生存期为 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）。 70% 的患者发生 3-4 级不良事件，其中最常见的是中性粒细胞减少症 (54%)。 5 名患者发生了免疫介导的不良事件（14%；甲状腺功能减退症，n = 3；肝炎，n = 2）。肿瘤浸润淋巴细胞密度较高（高于中位数）的患者表现出更好的 ORR（35% 对比 8%；p = 0.104）和无进展生存期（中位时间 7.3 个月对比 3.3 个月；p = 0.104）。 024）和总生存期（中位，未达到 vs. 21.5 个月；p = .027）。 avelumab 和吉西他滨的组合在一线治疗中取得进展的晚期 LMS 患者中显示出良好的疗效和可控的安全性。肿瘤浸润淋巴细胞密度可能是预测免疫治疗与化疗联合治疗反应的重要因素。© 2024 作者。 《癌症》由 Wiley periodicals LLC 代表美国癌症协会出版。

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.© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.