Final results of the TEMAVIR ANOCEF study in patients with unresectable glioblastoma

Irinotecan plus bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation versus chemoradiation for unresectable glioblastoma

A French team of investigators evaluated whether irinotecan and bevacizumab added to temozolomide-based chemoradiation would improve the prognosis of patients with unresectable glioblastoma. The study results show a trend towards improved progression-free survival and are presented by Dr B. Chauffert at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

This phase II, randomized trial enrolled 120 patients, aged 18 to 70 years with de novo unresectable glioblastoma, Karnofsky performance status > 50 and recursive partitioning analysis (RPA) class 5. Patients were randomized, 60 patients per arm, to receive four cycles of neo-adjuvant bevacizumab plus irinotecan prior to radiotherapy  with concurrent temozolomide and bevacizumab or to receive control treatment of concomitant temozolomide plus radiotherapy for 6 months.

Clinical factors were well balanced between arms and cross-over was allowed upon progression. An evaluation done at 16 months after the treatment showed longer progression-free survival (PFS)  in the treatment over the control arm; six and twelve months PFS were achieved by 65% and 31% of patients in the treatment arm compared with 41% and 18% of control patients. However, overall survival (OS) was similar between groups; six and twelve month OS were achieved by 75% and 48% compared with 72% and 50% of patients in the treatment and control arms, respectively.

Treatment-related serious adverse events of fatal brain haemorrhages occurred in 3 patients, 3 cases (one fatal) of biliary or digestive perforation/infection and 4 non-fatal thromboembolic episodes were seen in the treatment arm. In the control arm, two non-fatal cases of  biliary or digestive perforation/infection, 1 non-fatal pulmonary infection, 2 non-fatal cases of thromboembolism and 4 non-fatal cases of  thrombo- and/or neutropenia.

The authors concluded that the addition of irinotecan plus bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation showed a trend towards improved progression-free survival but did not improve six and twelve month overall survival compared to chemoradiation.