Piedmont Healthcare, Atlanta, Georgia, USA.
Case Western Reserve University & Case Comprehensive Cancer Center, Cleveland, Ohio, USA.
Neuro Oncol. 2024 Sep 5;26(9):1628-1637. doi: 10.1093/neuonc/noae058.
Immune checkpoint inhibitors (ICIs) have efficacy in several solid tumors but limited efficacy in glioblastoma (GBM). This study evaluated the safety of anti-CTLA-4 and anti-PD-1 ICIs alone or in combination in newly diagnosed GBM after completion of standard radiochemotherapy with the subsequent intent to test combinatorial ICIs in this setting.
The primary endpoint was dose-limiting toxicity (DLT) for adults with unifocal, supratentorial newly diagnosed GBM after resection and chemoradiation. Ipilimumab and nivolumab were tested separately and in combination with a planned expansion cohort dependent upon DLT results.
Thirty-two patients were enrolled at 9 institutions: 6 to each DLT assessment cohort and 14 to the expansion cohort. Median age: 55 years, 67.7% male, 83.9% White. Treatment was well tolerated with 16% Grade 4 events; the combination did not have unexpectedly increased toxicity, with no Grade 5 events. One DLT was seen in each single-agent treatment; none were observed in the combination, leading to expanded accrual of the combined treatment. The median follow-up was 19.6 months. For all patients receiving combination treatment, median overall survival (OS) and progression-free survival (PFS) were 20.7 and 16.1 months, respectively.
IPI and NIVO are safe and tolerable with toxicities similar to those noted with other cancers when given in combination with adjuvant temozolomide for newly diagnosed GBM. Combination IPI + NIVO is not substantially more toxic than single agents. These results support a subsequent efficacy trial to test the combination of ICIs in Phase II/III for patients with newly diagnosed GBM.
CLINICALTRIALS.GOV REGISTRATION: NCT02311920.
免疫检查点抑制剂（ICIs）在几种实体瘤中具有疗效，但在胶质母细胞瘤（GBM）中的疗效有限。本研究评估了抗 CTLA-4 和抗 PD-1 ICI 单独或联合用于标准放化疗后新诊断的 GBM 的安全性，随后计划在该环境中测试联合 ICI。
主要终点是接受单一治疗的单灶、幕上新诊断的 GBM 患者在切除和放化疗后的剂量限制毒性（DLT）。单独测试了伊匹单抗和纳武单抗，并根据 DLT 结果与计划的扩展队列联合测试。
9 家机构共招募了 32 名患者：6 名进入每个 DLT 评估队列，14 名进入扩展队列。中位年龄：55 岁，67.7%为男性，83.9%为白人。治疗耐受性良好，有 16%的 4 级事件；联合治疗未出现意外增加的毒性，无 5 级事件。单药治疗中有 1 例 DLT，联合治疗中未观察到 DLT，导致联合治疗的入组人数扩大。中位随访时间为 19.6 个月。所有接受联合治疗的患者，中位总生存期（OS）和无进展生存期（PFS）分别为 20.7 个月和 16.1 个月。
当 IPI 和 NIVO 与替莫唑胺联合用于新诊断的 GBM 辅助治疗时，与其他癌症中观察到的毒性相似，是安全且可耐受的。与单药治疗相比，联合应用 IPI+NIVO 并没有显著增加毒性。这些结果支持随后进行 II/III 期疗效试验，以测试联合 ICI 在新诊断的 GBM 患者中的应用。
NCT02311920。
