ABSTRACT Aim: VEGF or EGFR targeted monoclonal antibodies with chemotherapy demonstrated clinical activity in metastatic colorectal cancer (mCRC). Yet, combining these monoclonal antibodies in mCRC achieved adverse outcomes. However, erlotinib (E), an EGFR tyrosine kinase inhibitor, combined with bevacizumab (B) as maintenance (m) therapy after B-based induction therapy (IT) improved progression-free survival (PFS) (Tournigand, ASCO 2012). We report here the final results of the DREAM study. Methods: DREAM is a phase III trial in patients with unresectable mCRC. Pts without progression or surgery after a B-based IT were randomised to B (7.5 mg/kg q3w) or B (same dose) plus E (150 mg/d) as maintenance therapy until progression after stratification by centre, baseline ECOG status, ALP, LDH, induction chemotherapy (XELOX2-B vs mFOLFOX7-B or FOLFIRI-B), KRAS status, age, number of metastatic sites and tumour response (RR). Primary endpoint was mPFS from randomisation. Secondary endpoints were overall survival (OS), PFS from registration (r), response according to KRAS status, adverse events, curative resection, chemotherapy-free interval (CFI), and HR-QoL. Results: Among 701 registered pts, 452 were randomised for maintenance (B, 228; BE, 224). Median follow-up was 50 months. B arm vs BE arm, medians were: mPFS 4.9 vs 5.9 months (HR 0.77, CI 0.62-0.94; p = 0.012), rPFS 9.3 vs 10.2 months (HR 0.76, 95%CI 0.63-0.93; p = 0.007), mOS 22.0 vs 25.0 months (HR 0.80, CI 0.63-0.98; p = 0.034), rOS 26.9 vs 30.5 months (HR 0.80, CI 0.64-0.99; p = 0.040). All subgroups, including KRAS, had a benefit in OS. RR from baseline maintenance were B vs BE arm: all patients 11.5% vs 22.5% (OR 0.45, CI 0.25-0.79; p = 0.003), KRAS WT 15.4% vs 24% (OR 0.58, CI 0.27-1.19; p = 0.133), KRAS mut 8.3% vs 19.7% (OR 0.37, CI 0.12-1.04; p = 0.041). Patients in the B arm vs BE arm experienced less grade 3/4 diarrhea (0.9% vs 9.3%) and skin rash (0% vs 21.4%). Median time on therapy was 110 days in arm BE. Conclusions: Combination of erlotinib and bevacizumab as maintenance therapy significantly prolonged PFS and OS in patients with unresectable mCRC. The combination of anti-VEGF mab and EGFR tyrosine kinase inhibitor is active, even in mutated KRAS patients. Disclosure: B. Chibaudel: Roche, Sanofi; C. Tournigand: Roche, Sanofi; F. Bonnetain: Roche, Nestle, Merck; T. Andre: Roche; A. De Gramont: Roche, Sanofi. All other authors have declared no conflicts of interest.