Background: The DREAM phase III clinical trial aimed to assess the efficacy and tolerability of maintenance bevacizumab (B) plus erlotinib (E) after a bevacizumab-based induction therapy in patients with unresectable metastatic colorectal cancer (Tournigand C. et al. Lancet Oncol. 2015). The addition of E to B improved maintenance progression-free survival (PFS) (median B: 4.9months; median B+E: 5.4 months; Hazard Ratio (HR) = 0.78 [0.68-0.96], P = 0.036) and overall survival (OS). This study presents the results of health-related quality of life (HRQoL) data (secondary endpoint). Methods: HRQoL was assed using EuroQoL EQ-5D generic questionnaire before maintenance randomization (T0), at 2 (T1) and 4 months (T2). Analysis of baseline missing data profile was done comparing responders to non responders according to baseline patients’ characteristics and OS. The longitudinal analysis of the visual analogue scale (VAS) of the EQ-5D was done with a linear mixed model (LMM) by including the arm, the time and their interaction. Time to HRQoL deterioration (TTD) was defined as the time from randomization to the first deterioration of 5-point at least of the VAS score as compared to T0. Univariate cox regression analyses were performed to estimate HR of the treatment effect with its 95% confidence interval. Results: Between 2007 and 2011, 700 patients were included. After induction therapy, 452 patients without disease progression were randomized in B arm (N = 228) or B+E arm (N = 224). Among them, 111 patients (24.5%) completed the EQ-5D at T0, 78 (17.3%) at T1 and 54 (11.9%) at T2. Effects introduced in the LMM were not significant: arm effect (coeff = 0.93 (ref = Arm A), P = 0.83), time effect (coeff = 0.25, P = 0.88) and treatment by time interaction (coeff = 1.80, P = 0.42) reflecting a similar HRQoL among arms throughout its measurement. Median of TTD was 4.5 months (2.7-NA) for B vs. 4.1 months (2.3-NA) for B+E (HR = 1.46 [0.67-3.19], P = 0.34). Conclusions: These HRQoL results suggest that the added value of erlotinib to bevacizumab is not associated with a HRQoL deterioration, while it allows to improve maintenance PFS and OS. Clinical trial information: NCT00265824.