The DREAM Trial: Maintenance Therapy with Bevacizumab plus Erlotinib after Bevacizumab Induction Improves Outcomes
Monoclonal antibodies targeting vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) in combination with chemotherapy have demonstrated considerable clinical activity in patients with metastatic colorectal cancer (mCRC); however, combination therapy with these 2 monoclonal antibodies has been associated with adverse outcomes. Chibaudel and colleagues presented results of the DREAM study, which evaluated the use of the combination of the EGFR tyrosine kinase inhibitor erlotinib plus the anti-VEGF monoclonal antibody bevacizumab as maintenance therapy after bevacizumab-based induction therapy in patients with unresectable mCRC (Chibaudel et al. DREAM Trial. ESMO 2014: Abstract 497O).
In the DREAM trial, 452 eligible patients with mCRC and no disease progression or surgery after a bevacizumab-based induction therapy were randomized to receive bevacizumab 7.5 mg/kg every 3 weeks alone (n = 228) or in combination with erlotinib 150 mg daily (n = 224) as maintenance therapy until disease progression. The primary end point was maintenance progression-free survival (PFS) from randomization.
At a median follow-up of 50 months, median maintenance PFS was significantly prolonged in the combination arm compared with bevacizumab alone (5.9 vs 4.9 months), a 23% reduction in the risk for progression (hazard ratio [HR], 0.77; P = .012). Consistent with these results, the maintenance overall survival also showed significant improvement (24.9 vs 22.1 months; HR, 0.79; P = .034). A significant improvement in overall response rate was achieved with the combination maintenance therapy compared with bevacizumab monotherapy in all patients (22.5% vs11.5%; P = .003), KRAS wild-type subgroup (24% vs 15.4%; P = .133), and KRAS mutation-positive subgroup (19.7% vs 8.3%; P = .041). However, patients in the combination arm had higher rates of diarrhea of all grades (59% vs 14%) and skin rash (89% vs 9%) compared with bevacizumab alone.
Chibaudel and colleagues concluded that the combination of erlotinib and bevacizumab as maintenance therapy was an active treatment option for patients with unresectable mCRC after bevacizumab-based chemotherapy, even in those with KRAS mutations.