A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond six cycles in patients with glioblastoma (GEINO 14-01)

BACKGROUND: Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for six cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized, trial investigating whether extending adjuvant temozolomide for more than six cycles improved outcome. METHODS: Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after six cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of twelve cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS) and safety. (Clinicaltrials.gov NCT02209948). RESULTS: From August 2014 to November 2018, 166 patients were screened, seven of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P < 0.001), thrombocytopenia (P < 0.001), and nausea and vomiting (P = 0.001). CONCLUSIONS: Continuing temozolomide after six adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.