LBA24A RANDOMISED PHASE II STUDY OF CEDIRANIB WITH OR WITHOUT SRC INHIBITION (SARACATINIB) IN METASTATIC CLEAR CELL RENAL CANCER (RCC) PATIENTS RESISTANT TO VEGF TARGETED THERAPY

ABSTRACT Aim: Metastatic clear cell renal cancer (RCC) patients who are resistant to VEGF targeted therapy have a poor outcome. Further VEGF targeted therapy is a standard treatment option for these patients. It is speculated that SRC may play a role in this VEGF resistance. In the study cediranib (a VEGF tyrosine kinase inhibitor), was given with saracatinib (a SRC TKI) or placebo in VEGF resistant disease to test this hypothesis. Methods: This investigator led double bind randomised (1:1) phase II study recruited patients between 2010 and 2012 (n = 138). The primary endpoint was progression free survival (PFS) by RECIST v1.1. Toxicity was assessed using CTC V4. Patients received cediranib and saracatinib (CS) (n = 69) or cediranib and placebo (C) (n= 69). All patients had metastatic measurable RCC and had progression of disease on VEGF targeted therapy. Stratification factors included MSKCC prognostic score. Results: 15%,70%, 15% had MSKCC good, intermediate or poor risk disease respectively. Overall the characteristics of the 2 groups were well balanced. Partial responses were seen in 13% for C and 14.5% for CS respectively (p = NS). There was no significant difference in PFS [5.4 months (3.6-7.3 months) for C and 3.9 (2.4-5.3 months) for CS [HR 1.18 (0.94-1.48)], or overall survival [HR 1.28 (1.00-1.63)] for the 2 groups. The median overall survival for the whole cohort was 12.0 months (8.5-15.6 months. There was no significant difference in the frequency key adverse events. Discontinuation and dose reductions due to adverse events with C and CS occurred in 13%/8% and 19%/18% respectively. Biomarker analysis will be presented at the meeting. Conclusions: The addition of saracatinib to VEGF targeted therapy did not result in clinical benefit in VEGF resistant metastatic RCC. Cediranib appears to have modest activity in VEGF resistant disease. Disclosure: T. Powles: Research Funding from: AZ GSK Novartis. Honoraria from Pfizer GSK Novartis; R.J. Jones: Research funding from AZ; S. Chowdhury: GSK and Pfizer for speaking. All other authors have declared no conflicts of interest.