Ipilimumab with temozolomide vs. temozolomide alone after surgery and chemoradiotherapy in recently diagnosed glioblastoma: a randomized phase II clinical trial.

BACKGROUND: Glioblastoma confers a bleak prognosis, with median survival of less than a year. This trial evaluated whether addition of the CTLA-4 immune checkpoint inhibitor ipilimumab to standard therapy improves survival in patients with recently diagnosed glioblastoma. METHODS: Ipi-Glio was a stratified randomized, open-label, multicenter, academic phase II study. Patients with recently diagnosed de novo glioblastoma following completion of chemoradiotherapy were randomized 2:1 to ipilimumab + temozolomide (Arm A) vs temozolomide alone (Arm B), stratified to extent of surgery and MGMT promotor methylation. Primary endpoint was overall survival. Secondary endpoints included progression-free survival at 18 months, overall survival at 3 years, and toxicity (≥Grade 3). RESULTS: One hundred nineteen patients were randomized (79 to Arm A, 40 to Arm B). Patient characteristics (Arm A vs B): median age 57 vs 49 years; male sex 70 vs 65%, gross total resection 61 vs 60%, tumor MGMT promotor methylation 39 vs 40%. Median overall survival was 18 months (60% CI 16.0, 23.9) in Arm A vs 23.0 months (17.3, 26.4) in Arm B (adjusted HR 1.09, 60% CI 0.86,1.38, one-sided P = .62; logrank P = .75). Progression-Free Survival: 10.8 vs 12.5 months (Arm A vs B) (adjusted HR 1.34, 1.06-1.68, one-sided P = .86;logrank P = .42). Grade 3 or above adverse events: 53% Arm A vs 43% Arm B (P = .27). CONCLUSIONS: No benefit was observed with the addition of ipilimumab to temozolomide in patients with recently diagnosed glioblastoma following chemoradiotherapy. This study does not support further investigation of this regimen in this setting. TRIAL REGISTRATION: ISRCTN84434175 (www.isrctn.com/ISRCTN84434175).