C1-07: IPI-504, a novel HSP90 inhibitor is effective in EGFR T790M and Non-T790M Gefitinib-resistant Lung Cancer Cell Lines.

Abstract

Background: The Eastern Co-operative Oncology Group (ECOG) 4599 phase III trial demonstrated that the addition of bevacizumab to carboplatin/paclitaxel (CP) significantly improved overall survival and progression-free survival (PFS) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) [Sandler et al., NEJM 2006;355:2542-50]. Cisplatin/gemcitabine (CG) is a combination commonly used in Europe and other regions outside of the USA. In order to establish the efficacy of bevacizumab in combination with cisplatinbased doublets, the BO17704 trial investigated the effect of the addition of bevacizumab to CG on PFS in patients with advanced NSCLC. Methods: This randomised, placebo-controlled, multicentre 3-arm phase III study compared the efficacy of two doses of bevacizumab in combination with CG versus CG plus placebo. The primary endpoint was to demonstrate superiority in PFS in both bevacizumab-containing treatment arms versus the control regimen. Secondary endpoints were overall survival, response rate and safety. Eligibility criteria were histologically or cytologically documented previously untreated locally advanced, metastatic or recurrent non-squamous NSCLC; ECOG performance status 0-1; adequate haematological, renal and liver function; no brain metastases; no history of recent CTC grade ≥2 haemoptysis. Between February 2005 and August 2006, a total of 1,043 patients were randomised 1:1:1 to three treatment groups. One group received up to 6 cycles of C 80mg/m2 on day 1 and G 1,250mg/m2 on day 1 and day 8 every 3 weeks plus placebo (n=347). The second group received CG chemotherapy plus bevacizumab at a dose of 7.5mg/kg every 3 weeks (n=345), and the third group received CG chemotherapy plus bevacizumab at a dose of 15mg/kg every 3 weeks (n=351). Bevacizumab was to be administered until disease progression for both bevacizumab arms. Data cut-off was two months after the last patient was enrolled. Results: Bevacizumab at a dose of 7.5 or 15mg/kg every 3 weeks in combination with CG chemotherapy significantly prolonged PFS in patients with advanced NSCLC when compared with CG chemotherapy plus placebo. The treatment effects observed in the two bevacizumabcontaining arms were similar. No new safety signals associated with the use of bevacizumab were observed for either bevacizumab dose in this clinical setting. Conclusions: The trial met its primary endpoint. Final efficacy and safety results for each arm will be presented at the meeting.