Postoperative NEOadjuvant TEMozolomide followed by chemoradiotherapy versus upfront chemoradiotherapy for glioblastoma multiforme (NEOTEM) trial: Interim results

Background Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor survival rates despite current treatments. The standard of care (SOC) includes surgery, followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide (TMZ). This phase II trial assessed the safety and efficacy of neoadjuvant TMZ (nTMZ) before and during chemoradiotherapy in newly diagnosed GBM patients. Methods Newly diagnosed GBM patients who underwent maximal safe resection were randomized into 2 groups. One received nTMZ before standard chemoradiotherapy and adjuvant TMZ (intervention). The other received standard chemoradiotherapy followed by adjuvant TMZ (control). Primary endpoints were progression-free survival (PFS) at 6 and 12 months. Secondary endpoints included overall survival, radiological and clinical responses, and adverse events. Results Of 35 patients, 16 were in the intervention group and 19 in the control group. Median PFS was 9 months (95% CI: 3.93–14.06) versus 3 months (95% confidence interval [CI]: 1.98–4.01) in the control and intervention groups (P = .737), with a high progression rate (73.4%) during nTMZ treatment. The 6-month PFS rates were 58% versus 25% (P = .042), and 12-month PFS rates were 26% versus 25% (P = .390) in the control and intervention groups, respectively. Patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) and those with good performance status (PS) had significantly worse PFS with nTMZ. However, those who underwent larger extent of resection exhibited significantly better PFS with nTMZ. Adverse events were similar between groups. Conclusions Neoadjuvant TMZ before SOC chemoradiotherapy did not improve outcomes for newly diagnosed GBM patients and is unsuitable for those with unmethylated MGMT and good PS. However, It may benefit patients with near or gross total resection. Further research is needed to refine GBM treatment strategies.