STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma.

Methods

At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma.

在试验开始时，纳入标准包括：年龄≥18岁，高级别星形细胞瘤（2016年WHO中枢神经系统肿瘤分类[WHO CNS4]），在放疗和替莫唑胺(TMZ)后首次复发≥6个月，Karnofsky表现状态≥70，且没有与4级胶质母细胞瘤一致的影像学发现。

Random assignment (1:1) was stratified by isocitrate dehydrogenase (IDH) mutation, age, resection extent, and geography.

随机分配（1:1）根据异柠檬酸脱氢酶（IDH）突变、年龄、切除范围和地理位置进行分层。

Patients received eflornithine (2.8 g/m2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m2 once every 6 weeks).

患者接受依氟鸟氨酸（每8小时2.8克/平方米口服，连续2周后停药1周）+洛莫司汀（每6周90毫克/平方米口服），或洛莫司汀单药治疗（每6周110毫克/平方米）。

The primary end point was overall survival(OS).

主要终点是总生存（OS）。

Results

Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio[HR], 0.94).

在八个不同国家的74个地点随机分配的343名患者中，依氟鸟氨酸加洛莫司汀与洛莫司汀单药治疗的生存期没有差异（中位总生存期23.4个月对比20.3个月，风险比[HR]，0.94）。

Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH-mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival(PFS, 15.8 v 7.2 months, HR, 0.57).

在2021年WHO CNS5分类和分级变化后，对2024年定义的IDH突变型3级星形细胞瘤患者(n = 196)进行的亚组分析显示，与单独使用洛莫司汀相比，依氟鸟氨酸加洛莫司汀治疗组的中位总生存期（OS）有临床意义的改善（34.9个月对比23.5个月，风险比HR为0.64），以及中位无进展生存期（PFS，15.8个月对比7.2个月，HR为0.57）。

No differences were observed among patients with CNS grade 4 disease.

在CNS 4级疾病的患者中未观察到差异。

Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%).

与治疗相关的3级或更高级别的不良事件主要与可逆的骨髓抑制（eflornithine + lomustine组42%对比lomustine单药组29%的患者）和听力损害（24%对比0%）有关。

No new safety signals were identified.

未发现新的安全信号。

Conclusions

Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH-mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.

观察到临床意义显著的改善；在复发性 IDH 突变型 3 级星形细胞瘤患者中，依氟鸟氨酸加洛莫司汀使无进展生存期（PFS）翻倍，并改善了总生存（OS），但在 4 级肿瘤患者中未见此效果，这与依氟鸟氨酸的细胞静止作用机制一致，这些患者之前接受过放疗和替莫唑胺治疗。