The prognosis of patients with glioblastoma remains dismal, with median overall survival (OS) durations of ~15 months. New findings of a phase III trial indicate that adding lomustine to the standard treatment regimen improves the outcome of certain patients.

On the basis of evidence from a single-arm phase II study in 31 patients indicating an exclusive OS benefit, this phase III trial enrolled only patients with newly diagnosed MGMT promoter-methylated glioblastoma. In general, these patients have better responses to therapy and, thus, OS than those with MGMT promoter-unmethylated disease. After surgery, patients received standard daily radiotherapy either with daily temozolomide followed by six cycles of adjuvant temozolomide (n = 63), or with one course of lomustine and temozolomide chemotherapy (during the first week) followed by five additional cycles of lomustine and temozolomide (n = 66).

Median OS was 48.1 months with the lomustine–temozolomide regimen versus 31.4 months with temozolomide alone (HR 0.60, 95% CI 0.35–1.03; P = 0.0492). In both groups, the median progression-free survival was 16.7 months (P = 0.4113).

The frequency of grade 3–4 adverse events occurring up to 30 days after the end of study treatment was higher with lomustine–temozolomide than with temozolomide alone (59% versus 51%). No treatment-related deaths were reported. Notably, lower proportions of patients in the experimental arm received all six courses of chemotherapy (39% versus 60%) and the maximum temozolomide dose (38% versus 67%).

The investigators acknowledge that further studies in large cohorts are needed to confirm their findings. However, the current data indicate that the lomustine–temozolomide regimen has the potential to become a new standard of care.