Background: In absence of oncogenic driver chemotherapy (CT) for advanced non-squamous non-small cell lung cancer (NS-NSCLC) remains palliative with similar efficacy and survival among different regimens. Histotype, maintenance therapy (m) and quality of life (QoL) have been explored to improve patients (pts) outcome. ERACLE trial (NCT01303926), a QoL-oriented phase III trial was designed to compare the QoL for two CT regimens. Methods: Pts with stage IIIB/IV NS-NSCLC (ECOG 0/1) were randomized (1:1) to receive first-line CT. ARM A received 6 cycles of Cisplatin (C) (75 mg/m²) - Pemetrexed (P) (500 mg/m²) q3w, followed by mP (500 mg/m²) while ARM B received Carboplatin (Cb) AUC 6 - Paclitaxel (T) 200 mg/m²plus Bevacizumab (Be) 15 mg/kg q3w for 6 cycles and mBe 15 mg/kg. Both treatments were administered until progression, unacceptable toxicity or death. Stratification was based on Study Centre and disease stage. Co-Primary endpoints were EQ5D Index (EQ5D-I) and EQ5D-VAS (Euro-QoL questionnaire) at 12 weeks during m. Secondary endpoints were QoL over time, activity and safety of CT arms. A sample of 49 pts per arm (not progressed during initial CT and during m therapy for at least 12 weeks) will have 91% chance to have 12-point Minimal Interesting Difference (MID) between arms for EQ5D-VAS, and 87% chance to find 0.137 MID between arms for EQ5D-I. It is assumed that about 20% of pts in both arms experienced a PD before to evaluate primary endpoint. The study sample was then increased to 118. Results: From 1/2011 to 3/2012, 118 pts were randomized to CP (n=60) or CbTBe (n=58). Baseline demographics were well balanced across arms; overall 74% male, 79% PS 0 and 94% stage IV. Treatment differences (mean change from baseline), EQ5D-VAS = 1.82 (95%CI -8.60 to 12.24; P=0.73), EQ5D-I = 0.15 (95%CI 0.01 to 0.29), favoured arm A. Conclusions: CP-mP showed better (over the MID) health profile (EQ5D-I) at 12 weeks as compared to CbBe-mBe. EQ5D-VAS didn’t find any significant difference between treatment arms. Clinical trial information: NCT01303926.