title: Salvage-targeted kidney cancer therapy in patients progressing on high-dose interleukin-2 immunotherapy: the UCLA experience.
abstract: OBJECTIVE
  To analyze the outcomes of patients with metastatic renal cell carcinoma treated with salvage-targeted therapy after progressing on high-dose interleukin (IL)-2 immunotherapy in a tertiary referral center.
  
  
  METHODS
  A retrospective nonrandomized cohort consisting of 286 patients with metastatic renal cell carcinoma treated from 2003 to 2010 was analyzed from the University of California, Los Angeles (UCLA) Kidney Cancer database. All patients underwent cytoreductive nephrectomy, and 21 patients received salvage-targeted therapy after progression on high-dose IL-2, whereas 111 patients received targeted therapy alone. The remaining 154 patients had other treatment combinations or experimental targeted therapy agents only. Since 2003, selection of patients for high-dose IL-2 was increasingly based on clinical, pathologic, and molecular criteria (UCLA CPM criteria). Disease-specific survival was calculated from diagnosis of metastatic renal cell carcinoma.
  
  
  RESULTS
  Patients selected according to UCLA CPM criteria and treated with salvage-targeted therapy after progressing on high-dose IL-2 experienced a significantly greater disease-specific survival (median not reached) than those treated with targeted therapy alone (30 months; P = 0.004). Since 2006, all high-dose IL-2 patients met the UCLA CPM criteria and were able to receive salvage-targeted therapy upon progression. Disease-specific survival calculated from initiation of targeted therapy was comparable for patients treated with salvage-targeted therapy after progression on high-dose IL-2 (34 months) versus first-line targeted therapy (26 months; P = 0.175).
  
  
  CONCLUSIONS
  Patients selected for high-dose IL-2 based on UCLA CPM criteria and treated with salvage-targeted therapy upon progression have achieved outstanding disease-specific survival. Our data suggest a new algorithm for carefully selected patients with metastatic renal cell carcinoma based on UCLA CPM criteria to receive first-line high-dose IL-2 while reserving their option for salvage-targeted therapy with uncompromised efficacy upon progression.
authors.affiliation: Institute of Urologic Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USA.
authors.forename: Frédéric D
authors.initials: FD
authors.lastname: Birkhäuser
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
authors.forename: Edward N
authors.initials: EN
authors.lastname: Rampersaud
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pouliot
authors.forename: Nazy
authors.initials: N
authors.lastname: Zomorodian
authors.forename: Joseph
authors.initials: J
authors.lastname: Riss
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2