REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours
Mené sur 19 patients atteints d'une tumeur solide, cet essai français multicentrique de phase I évalue la dose optimale de bevacizumab en combinaison avec une radiothérapie du cerveau entier pour traiter des métastases cérébrales
Background : Brain metastases (BM) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. Patients and methods : In this multicentre single-arm phase I study with a 3+3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses (5, 10 and 15 mg/kg every 2 weeks at dose levels [DL] 0, 1 and 2, respectively) and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. Results : Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for 5 and 9 patients across all DLs, respectively, including 3 and 6 patients (including one patient with both, so 8 patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2, and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in 2 deaths. The remaining patient died from extracranial disease progression. Conclusion : Bevacizumab combined with WBRT appears to be a tolerable treatment for BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance.