LBA24 - A randomised phase II study of cediranib with or without SRC inhibition (saracatinib) in metastatic clear cell renal cancer (RCC) patients resistan...

Date 29 September 2014
Event ESMO 2014
Session Genitourinary tumours, non prostate
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Presenter Thomas Powles
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors T.B. Powles1, R. Hawkins2, C. Ralph3, J. Larkin4, R.J. Jones5, S. Chowdhury6, E. Boleti7, K. Fife8, A. Bahl9, S. Crabb10, A. Webb11, O. Din12, J. Dunlop13, R. Hill13, T. Geldart14, D. McLaren15, P. Nathan16
  • 1Ecmc/qmul, Barts Cancer Institute, EC1M 6BQ - London/GB
  • 2Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 3Medical Oncology, St James’s Institute of Oncology, Leeds/GB
  • 4Medicine, Royal Marsden Hospital NHS Foundation Trust, - - London/GB
  • 5Medical Oncology, Beatson West of Scotland Cancer Centre Gartnavel General Hospital, G12 0YN - Glasgow/GB
  • 6Department Of Medical Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 7Oncology, Royal Free Hospital, London/GB
  • 8Oncology, Cambridge University Hospital, Cambridge/GB
  • 9Clinical Oncology, Bristol Haematology and Oncology Centre, BS2 8ED - Bristol/GB
  • 10Oncology, Southampton University, London/GB
  • 11Oncology, Royal Sussex County, BN2 5BE - Brighton/GB
  • 12Oncology, Weston Park Hospital, S10 2SJ - Sheffield/GB
  • 13Cactus Partners, Beatson West of Scotland Cancer Center, G12 0YN - Glasgow/GB
  • 14Medical Oncology, Royal Bournemouth Hospital, BH7 7DW - Bournemouth/GB
  • 15Oncology, Western General Hospital, EH4 2XU - Edinburgh/GB
  • 16Cancer Services, Mount Vernon Cancer Centre, Northwood/GB

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.