LBA25_PRCIRCCA: A RANDOMISED DOUBLE BLIND PHASE II TRIAL OF CARBOPLATIN-PACLITAXEL PLUS CEDIRANIB VERSUS CARBOPLATIN-PACLITAXEL PLUS PLACEBO IN METASTATIC/RECURRENT CERVICAL CANCER. (CRUK GRANT REF: C1256/A11416)

ABSTRACT Aim: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly (response rates 20-30%) to conventional chemotherapy with an overall survival of less than a year. High tumour angiogenesis along with high levels of intratumoural vascular endothelial growth factor (VEGF) are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGF receptors1,2&3. Methods: Patients were randomised (1:1) to receive carboplatin AUC5 + paclitaxel 175mg/m2 3 weekly for a maximum of 6 cycles plus 20mg cediranib daily (arm A) or placebo (arm P) until disease progression. Plasma VEGFR-2 levels were measured at baseline and at 28 days into chemotherapy. The primary end-point was progression- free survival (PFS). Secondary end-points included changes in sVEGFR-2 from baseline to day 28, overall survival (OS), response, toxicity and quality of life. The study has approximately 80% power (20% 1-sided) to detect a 60% increase in median PFS from 4 to 6.4 months. Results: 69 patients were randomised (35 P; 34 A) during 2010-12, 13% with local relapse only, 30% with extra pelvic metastases and 57% with both. 83% had 1 line of previous treatment. 79% completed 6 cycles of chemotherapy. 22% stopped P and 17% stopped A for treatment related reasons. Median PFS (wks; 80% CI) is 30 (29, 31) on P versus 35 (32, 38) on A (hazard ratio A/P [HR] 0.61; 80% CI: (0.41, 0.89); P = 0.046). Median change in log10 sVEGFR-2 from baseline was .067 (n = 22) on P compared to -.036 (n = 18) on A (P Conclusions: PFS, inhibition of VEGFR-2 receptor and response rate were all significantly increased on arm A. This was accompanied by a manageable toxicity increase (diarrhoea and hypertension). Acknowledgements: This research was supported by CRUK,ECMC funding and conducted with support from Investigator-Sponsored Study Collaboration between AstraZeneca and the NCRN. Study Sponsors: NHS Greater Glasgow & Clyde and University of Glasgow. Disclosure: C. Gourley: Personal (advisory board membership) and non-personal specific and non-specific interests in AstraZeneca, GlaxoSmithKline and Roche; S. Banerjee: Conflict of Interest - AstraZeneca (not directly financially remunerated); R. Lord: Has acted on advisory boards for AstraZeneca but not in relation to Cediranib. All other authors have declared no conflicts of interest.