OBJECTIVES - Second targeted therapies for mRCC include mammalian target of rapamycin inhibitors (mTORi) and tyrosine kinase inhibitors (TKI). 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.
Current medical research and opinion. 2016 Jan 08 [Epub ahead of print]
Nicholas J Vogelzang, Sumanta K Pal, James E Signorovitch, William M Reichmann, Nanxin Li, Chelsey Yang, Zhimei Liu, Jose Ricardo Perez, Eric Jonasch
a US Oncology Research, Comprehensive Centers of Nevada , Las Vegas , NV , USA. , b City of Hope Comprehensive Cancer Center , Duarte , CA , USA. , c Analysis Group, Inc. , Boston , MA , USA. , c Analysis Group, Inc. , Boston , MA , USA. , c Analysis Group, Inc. , Boston , MA , USA. , c Analysis Group, Inc. , Boston , MA , USA. , d Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA. , d Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA. , e MD Anderson Cancer Center , Houston , TX , USA.