Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naïve patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704

Abstract

LBA7514 Background: The ECOG 4599 phase III trial demonstrated that the addition of bevacizumab (B) to carboplatin/paclitaxel improved overall and progression-free survival (PFS) in patients (pts) with advanced NSCLC [Sandler et al. NEJM 2006]. Cisplatin/gemcitabine (CG) is a common combination in regions outside of the US. Methods: This randomised, placebo-controlled phase III study compared two doses of B plus CG versus CG plus placebo. The primary endpoint was PFS; secondary endpoints include overall survival, response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non- squamous NSCLC; ECOG PS 0–1; no brain metastases. Between 2/05 and 8/06 1,043 pts were randomised to: C 80mg/m 2 on d1 and G 1,250mg/m 2 on d1 and d8 every 3 wks for up to 6 cycles plus B continued to progression at 7.5mg/kg every 3 wks, or 15mg/kg every 3 wks or placebo. The study was designed to include the number of patients required to observe a 30% reduction in the risk of a PFS event in the B arms compared with control using a two-sided logrank test (a=2.5%) with 80% power. Results: PFS was significantly prolonged as analysed both in a primary analysis (without censoring for non-protocol anti-neoplastic therapy [NPT] prior to progression) and in a prespecified analysis with censoring for NPT. The RR and response duration were also increased. Overall survival is immature due to short duration of follow up. Conclusions: Both doses of B significantly improved PFS and RR, consistent with the results of the earlier phase III trial E4599. No unexpected safety signals were detected. [Table: see text] [Table: see text]