Rutkowski Piotr Lukasz, Klimczak Anna, Teterycz Pawel, Pantaleo Maria Abbondanza, Switaj Tomasz, Rogala Pawel, Poleszczuk Jan, Nannini Margherita, Nigro Maria Concetta, Kozak Katarzyna
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw 02-781, Poland.
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw 02-781, Poland; Digital Medicine Centre Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw 02-781, Poland.
Eur J Cancer. 2025 Jul 25;225:115565. doi: 10.1016/j.ejca.2025.115565. Epub 2025 Jun 6.
Treatment options for patients with advanced gastrointestinal stromal tumor (GIST) after failure of standard therapies with tyrosine kinase inhibitor (TKI) remain very limited. As vascular endothelial growth factor (VEGF) inhibitors are considered to have immunomodulatory effects, we hypothesized that the combination of VEGF and PD-L1 inhibitors may have a synergistic effect and enhance the efficacy of both therapies.
AXAGIST was a phase II trial evaluating the efficacy and safety of avelumab 10 mg/kg iv Q2W in combination with axitinib 5 mg po BID in patients with unresectable/metastatic GIST after failure of standard therapy. The primary endpoint was progression-free survival (PFS) at 3 months based on RECIST 1.1 criteria. Secondary endpoints included PFS, overall survival (OS), overall response rate, and safety.
Of the 58 patients enrolled, 56 patients were evaluable for safety and efficacy. Median age was 60 years (range 18-80), and 30 patients (53.4 %) had received three prior lines of TKIs. Median follow-up was 27.4 months. The best response was partial response in 5 patients (8.9 %), stable disease in 34 patients (60.7 %), and progressive disease in 17 patients (30.4 %). Among patients with partial response, the median duration of response was 18.5 months (95 %CI, 18.3-NA). The PFS rate at 3 months was 57.1 %. Median PFS and OS were 4.6 months (95 %CI, 2.9-6.4) and 14.2 months (95 %CI, 9.2-26.3), respectively. Adverse events occurred in 94.6 % of patients, while 30.4 % experienced grade 3 or higher adverse events.
The results of the largest trial on the combination of targeted therapy and immunotherapy in pretreated GIST show the promising efficacy of this novel therapeutic approach in a subset of patients.
对于标准酪氨酸激酶抑制剂（TKI）治疗失败后的晚期胃肠道间质瘤（GIST）患者，治疗选择仍然非常有限。由于血管内皮生长因子（VEGF）抑制剂被认为具有免疫调节作用，我们推测VEGF和PD - L1抑制剂联合使用可能具有协同作用，并提高两种疗法的疗效。
AXAGIST是一项II期试验，评估在标准治疗失败后不可切除/转移性GIST患者中，阿维鲁单抗10 mg/kg静脉注射每2周一次联合阿昔替尼5 mg口服每日两次的疗效和安全性。主要终点是基于RECIST 1.1标准的3个月无进展生存期（PFS）。次要终点包括PFS、总生存期（OS）、总缓解率和安全性。
在纳入的58例患者中，56例患者可进行安全性和疗效评估。中位年龄为60岁（范围18 - 80岁），30例患者（53.4%）曾接受过三线TKI治疗。中位随访时间为27.4个月。最佳反应为5例患者部分缓解（8.9%），34例患者疾病稳定（60.7%），17例患者疾病进展（30.4%）。在部分缓解的患者中，中位缓解持续时间为18.5个月（95%CI，18.3 - NA）。3个月时的PFS率为57.1%。中位PFS和OS分别为4.6个月（95%CI，2.9 - 6.4）和14.2个月（95%CI，9.2 - 26.3）。94.6%的患者发生不良事件，30.4%的患者经历3级或更高等级的不良事件。
这项针对预处理GIST患者的靶向治疗与免疫治疗联合的最大规模试验结果显示，这种新型治疗方法在一部分患者中具有有前景的疗效。
