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Abstract
Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies.
Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI.
Results Included patients (n = 325 for everolimus and n = 127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with <6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup.
Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors.
Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.
Declaration of funding
Funding for this research was provided by Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Author contributions: All authors participated in the design of the study and contributed to the manuscript development. Data were collected by Analysis Group (J.E.S., W.M.R., N.L., and C.Y.) and analyzed and interpreted in collaboration with all other authors. The authors prepared manuscript drafts with editorial assistance from a professional medical writer. All the authors vouch for the accuracy and completeness of the data reported and the adherence of the study to the protocol, and all the authors made the decision to submit the manuscript for publication.
Declaration of financial/other relationships
N.J.V. has disclosed that he has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, Roche, has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen, and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. S.K.P. has disclosed that he has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. J.E.S., W.M.R., N.L., and C.Y. have disclosed that they are employees of Analysis Group Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation for this project. Z.L. and J.R.P. have disclosed that they are employees of Novartis Pharmaceuticals Corporation and may own stock/stock options. E.J. has disclosed that he has been a consultant for Novartis, GSK, and Pfizer as well as received grant funding from Exelixis, GSK, Novartis, and Pfizer.
The CMRO peer reviewer on this manuscript has no relevant financial or other relationships to disclose.
Acknowledgments
Medical writing assistance was provided by Shelley Batts PhD, an employee of Analysis Group Inc.