title: Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review.
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.
authors.affiliation: a US Oncology Research, Comprehensive Centers of Nevada , Las Vegas , NV , USA ;
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: b City of Hope Comprehensive Cancer Center , Duarte , CA , USA ;
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: c Analysis Group Inc. , Boston , MA , USA ;
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.affiliation: c Analysis Group Inc. , Boston , MA , USA ;
authors.forename: William M
authors.initials: WM
authors.lastname: Reichmann
authors.affiliation: c Analysis Group Inc. , Boston , MA , USA ;
authors.forename: Nanxin
authors.initials: N
authors.lastname: Li
authors.affiliation: c Analysis Group Inc. , Boston , MA , USA ;
authors.forename: Chelsey
authors.initials: C
authors.lastname: Yang
authors.affiliation: d Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA ;
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: d Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA ;
authors.forename: Jose Ricardo
authors.initials: JR
authors.lastname: Perez
authors.affiliation: e MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D057186:Comparative Effectiveness Research; D018572:Disease-Free Survival; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007191:Indazoles / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; D000077784:Axitinib; D000077210:Sunitinib; D020123:Sirolimus
keywords: Axitinib; comparative effectiveness; everolimus; metastatic renal cell carcinoma; overall survival; progression-free survival; targeted therapies