title: Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line therapy in patients with metastatic renal cell carcinoma after the failure of first-line VEGF TKI.
abstract: Sequential therapy is a standard strategy used to overcome the limitations of targeted agents in metastatic renal cell carcinoma. It remains unclear whether a mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line therapy after first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) has failed than the alternative, VEGF TKI. A clinical database was used to identify all patients with renal cell carcinoma who failed at first-line VEGF TKI and then treated with second-line VEGF TKI or mTOR inhibitors in the Asan Medical Center. Patient medical characteristics, radiological response and survival status were assessed. Of the 83 patients who met the inclusion criteria, 41 received second-line VEGF TKI [sunitinib (n = 16) and sorafenib (n = 25)] and 42 were treated with mTOR inhibitors [temsirolimus (n = 11) and everolimus (n = 31)]. After a median follow-up duration of 23.9 months (95 % CI, 17.8-30.0), progression-free survival was 3.0 months for both groups [hazard ratio (HR, VEGF TKI vs. mTOR inhibitor) = 0.97, 95 % CI 0.59-1.62, P = 0.92]. Overall survival was 10.6 months for the VEGF TKI group and 8.2 months for the mTOR inhibitor group (HR = 0.98, 95 % CI 0.57-1.68, P = 0.94). The two groups did not differ significantly in terms of disease control rate (51 % for VEGF TKI and 59 % for mTOR inhibitor, P = 0.75). Second-line VEGF TKI seems to be as effective as mTOR inhibitors and may be a viable option as a second-line agent after first-line anti-VEGF agents have failed.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Kwonoh
authors.initials: K
authors.lastname: Park
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Inkeun
authors.initials: I
authors.lastname: Park
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Ahn
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Shin
authors.initials: S
authors.lastname: Ahn
authors.forename: Cheryn
authors.initials: C
authors.lastname: Song
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Hong
authors.forename: Choung-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Hanjong
authors.initials: H
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000068338:Everolimus; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; 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; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage; D016879:Salvage Therapy / Q000379:methods*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077157:Sorafenib; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; C401859:temsirolimus; D000068338:Everolimus; D000077157:Sorafenib; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus