Abstract
BACKGROUND
Novel therapies are needed in newly diagnosed glioblastoma as nearly all patients experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ), including patients with tumors with methylated MGMT promoter, a positive prognostic factor and predictor of benefit with TMZ. Here, we report the final analysis of progression-free survival (PFS), overall survival (OS), and safety from an international randomized, single-blind phase-3 study of nivolumab (NIVO)+RT+TMZ in patients with newly diagnosed glioblastoma with methylated/indeterminate MGMT promoter (CheckMate 548; NCT02667587).
METHODS
Patients (N=716) aged ≥ 18y were randomized 1:1 regardless of tumor PD-L1 expression to NIVO (240 mg Q2W×8, then 480 mg Q4W) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 QD during RT, then 4-week break, then 150–200 mg/m2 QD on days 1–5 of every 28-day cycle for 6 cycles) or placebo (PBO)+RT+TMZ. The dual-primary endpoints were PFS by blinded independent central review and OS, both overall and without baseline corticosteroids.
RESULTS
As of December 22, 2020, median PFS was 10.6 months (95% CI, 8.9–11.8) with NIVO+RT+TMZ and 10.3 months (95% CI, 9.7–12.5) with PBO+RT+TMZ (HR, 1.06 [95% CI, 0.90–1.25]). Median OS was 28.9 months (95% CI, 24.4–31.6) with NIVO+RT+TMZ and 32.1 months (95% CI, 29.4–33.8) with PBO+RT+TMZ (HR, 1.10 [95% CI, 0.91–1.33]). Among patients without baseline corticosteroids, median OS was 31.3 months (95% CI, 28.6–34.8) with NIVO+RT+TMZ and 33.0 months (95% CI, 31.0–35.1) with PBO+RT+TMZ (HR, 1.12 [95% CI, 0.87–1.43]). Grade 3–4 treatment-related adverse events were 52.4% and 33.6% with NIVO+RT+TMZ and PBO+RT+TMZ, respectively.
CONCLUSIONS
NIVO added to RT+TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated/indeterminate MGMT promoter. No new safety signals were observed with NIVO. The role of immunotherapy in this treatment landscape remains an area for further investigation.
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial