Comparative outcomes of everolimus, temsirolimus and sorafenib as second targeted therapies for metastatic renal cell carcinoma: a US medical record review

Objective: To compare outcomes of metastatic renal cell carcinoma (mRCC) patients treated with everolimus, temsirolimus, and sorafenib following initial treatment with a tyrosine kinase inhibitor (TKI) in community and academic practices throughout the US. Research design and methods: Medical records of mRCC patients who received everolimus, temsirolimus or sorafenib as their second therapy following a TKI were retrospectively reviewed from a nationally representative panel of oncologists. Overall survival (OS) and progression-free survival (PFS) of second targeted therapies were compared using multivariable Cox proportional hazard models, with adjustment for demographics, disease severity and prior treatments. Results: A total of 233, 178, and 123 mRCC patients receiving everolimus, temsirolimus, and sorafenib, respectively, as second targeted therapies were included. Eighty-six percent used sunitinib and the remainder used sorafenib or pazopanib as their initial TKI. After adjusting for baseline characteristics, everolimus was associated with significantly prolonged OS (hazard ratio [HR] 0.60; Cl 0.42-0.85; p = 0.004) and PFS (HR 0.73; Cl 0.54-0.97; p = 0.032) compared to temsirolimus. Everolimus was associated with significantly longer OS (HR 0.66; Cl 0.44-0.99; p = 0.045) and numerically longer PFS compared to sorafenib. No significant differences were observed between temsirolimus and sorafenib. Limitations: Despite adjustment for multiple patient characteristics, comparisons between treatment groups may be confounded by unobserved factors in this retrospective observational study. Tolerability outcomes were not collected. Conclusions: In this retrospective, non-randomized study of mRCC patients with prior TKI treatment, everolimus was associated with significantly prolonged OS and PFS compared to temsirolimus and significantly prolonged OS compared to sorafenib.