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

Abstract

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; CI 0.42–0.85; p = 0.004) and PFS (HR 0.73; CI 0.54–0.97; p = 0.032) compared to temsirolimus. Everolimus was associated with significantly longer OS (HR 0.66; CI 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.

Keywords::

• Molecular targeted therapy
• Progression-free survival
• Renal cell carcinoma
• Survival

Transparency

Declaration of funding

This research was partially funded by Novartis Pharmaceuticals Corporation. Novartis develops and markets drugs to treat various conditions, including metastatic renal cell carcinoma.

Declaration of financial/other relationships

M.K.W. has reported that he had a consultancy role with, and/or received honoraria from Bristol Myers Squibb, Merck, and Pfizer. D.J.G. has reported that he had a consultancy role with, and/or received honoraria or research funding from Bayer, Novartis, and Pfizer. X.W. and Z.L. are employees of Novartis Pharmaceuticals Corporation and own stock/options in Novartis. H.Y., J.E.S., N.S.L., and C.Z.Q. are employees of Analysis Group Inc., which was contracted and funded by Novartis Pharmaceuticals Corporation to partner on this research.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgment

Previous presentation: This study has been presented at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA, 31 May–4 June 2012.