Objectives First-line pemetrexed-cisplatin (Pem-Cis) induction therapy followed by Pem maintenance, and first-line bevacizumab- (Bev-) based therapy are treatment options for patients with advanced non-squamous NSCLC. This study explored efficacy and safety of first-line induction Pem-Cis + Bev followed by maintenance Pem + Bev. Materials and methods Patients with ECOG performance status (PS) 0–1 were scheduled to receive four cycles Pem 500 mg/m 2 , Cis 75 mg/m 2 , and Bev 7.5 mg/kg, given every 21 days. In absence of progressive disease (PD) and if ECOG-PS ≤1, patients could continue Pem + Bev maintenance until PD or unacceptable toxicity. All patients received vitamin supplementation as per Pem label. Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and toxicity. Results 109 patients received induction therapy (median age 61 yrs, ECOG-PS 0/1 54/46%, stage IIIB/IV 9/91%, adenocarcinoma 91%), 72 patients (66.1%) started maintenance therapy. Median (maximum) numbers of cycles were 4 (4) for Cis and 8 (34) for Pem + Bev. Overall, median PFS and OS were 6.9 (90%CI 5.7–8.3) and 14.7 (95%CI 11.5–19.7) months. For patients starting maintenance therapy, median (95%CI) PFS and OS were 9.4 (7.2–11.5) and 19.7 (14.9–25.9) months. Overall response and disease control rates were 42.2% and 67.9%, respectively. Two patients died from study-treatment related toxicity (gastrointestinal hemorrhage, aspiration pneumonia; both during induction therapy). Most common G3/4 toxicities were neutropenia (25.7%) and fatigue (14.7%); hypertension was less common (5.5%). Conclusion Patients with advanced NS-NSCLC eligible for Bev-treatment may derive clinical benefit at acceptable toxicity from the addition of Bev to both Pem-Cis induction and Pem maintenance therapy; however, this is not an approved combination regimen. [ABSTRACT FROM AUTHOR]