Saracatinib, an Src inhibitor, did not improve the efficacy of cediranib, a vascular endothelial growth factor (VEGF) targeted therapy, in patients with relapsed metastatic renal cell carcinoma (mRCC), a study published online ahead of print in the journal Annals of Oncology has shown.1

Because preclinical trials suggest that Src proteins play a role in the development of resistance to VEGF targeted therapy in clear cell RCC, researchers sought to evaluate this hypothesis by comparing cediranib plus saracatinib with cediranib plus placebo.

For the phase 2 study, researchers enrolled 138 patients with mRCC who experienced disease progression after 1 or more VEGF targeted therapies. Participants were randomly assigned to receive cediranib 30 mg once daily and saracatinib 175 mg once daily, or cediranib 45 mg once daily and placebo. Biomarker analyses were also conducted for SRC, FAK, VHL, PTB1b, and HIF2α levels.

Results showed that 13.0% of patients in the cediranib group and 14.5% of patients in the combination group achieved partial responses (P > .05). Researchers also observed no significant difference in progression-free survival (HR, 1.18; 95% CI, 0.94 – 1.48) or overall survival (HR, 1.28; 95% CI, 1.00 – 1.63) between the 2 arms.


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There was no significant difference in the frequency of key adverse events, dose reductions, or treatment discontinuations.

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Furthermore, the study demonstrated no prognostic association between the evaluated biomarkers and progression-free or overall survival; however, there was a correlation between FAK overexpression and overall survival benefit (HR, 2.29; 95% CI, 1.09 – 4.82; P > .05) for saracatinib plus cediranib.

Reference

  1. Powles T, Brown J, Larkin J, et al. A randomised, double-blind phase II study evaluating cediranib vs cediranib and saracatinib in patients with relapsed metastatic clear cell renal cancer (COSAK) [published online ahead of print January 22, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw014.