A double blind phase II study of BIBF 1,120 in patients suffering from relapsed advanced non-small cell lung cancer (NSCLC)

7635 Background: Vascular endothelial-(VEGF), platelet derived- (PDGF), and fibroblast growth factor (FGF) with their receptors compose critical cellular pathways controlling angiogenesis. BIBF 1120 is an oral potent triple angiokinase inhibitor targeting VEGFR, PDGFR, FGFR kinases. Methods: In this double blind multi-center trial, patients with an ECOG score of 0–2 with locally advanced or metastatic (stage IIIB/IV) relapsed NSCLC after failure of first or second line chemotherapy were randomly assigned to daily treatment with 2x250 mg or 2x150 mg of BIBF 1,120 until progression. In the event of dose limiting toxicity, a single dose reduction to open label treatment with 2x150 or 2x100 mg of BIBF 1,120 was allowed. Patients with stable brain metastases or squamous cell carcinoma were not excluded. Primary endpoints were progression free survival (PFS) and objective tumor response (RECIST, determined every 6 weeks). Results: Seventy three of 74 patients enrolled received BIBF 1120 (61% males, median age: 64 years, range 36–80). The most common histology was adenocarcinoma (55%), followed by squamous cell carcinoma (23%). The median PFS of all patients (n= 73) was 1.6 months without significant difference between both treatment arms. The stable disease rate was 48% without objective tumour responses. However, patients with an ECOG performance status of 0 or 1 (n= 57) had a median PFS of 2.9 months and a three- and 5 months PFS rate of 46% and 31%, without any difference between both treatment arms. The stable disease rate was 59%. Patients treated with 2x250 mg per day had more dose limiting CTCAE Grade 3 and 4 toxicities compared with patients treated with 2x150 mg (27% versus 2.8%, p=0.006, two-sided Fisher-test). The most frequent adverse events irrespective of relatedness observed in 73 patients were of CTCAE Grade 1 or 2 and included nausea (41%), diarrhoea (41%), vomiting (33%), fatigue (29%) and abdominal pain (22%). Grade 3 and 4 toxicities included nausea (8%), diarrhoea (7%), vomiting (4%), abdominal pain (4%) and AST and/or ALT elevations (5.4%). Conclusions: BIBF 1120 is safe and well tolerated and showed promising efficacy data in ECOG 0–1 patients. A high disease control rate of 59% could be observed. Table: see text