title: Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM.
abstract: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2).
  
  
  
  Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in ProleukinRObservational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015.
  
  
  
  Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2.
  
  
  
  HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients.
authors.affiliation: Department of Medicine, Loyola University Medical Center, Maywood, IL.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Michael K K
authors.initials: MKK
authors.lastname: Wong
authors.affiliation: Department of Surgery, Rutgers Cancer Center Institute of New Jersey, New Brunswick, NJ.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.affiliation: Department of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Daniels
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.affiliation: Department of Medicine, St. Luke's University Health Network and Temple University, Easton, PA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Agarwala
authors.affiliation: Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH.
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Stewart
authors.affiliation: Department of Medicine, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.affiliation: Department of Medicine, Providence Portland Medical Center, Portland, OR.
authors.forename: Brendan
authors.initials: B
authors.lastname: Curti
authors.affiliation: Department of Medicine, University of Colorado Cancer Center, Aurora, CO.
authors.forename: René
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Department of Medicine, Mount Sinai Medical Center, Miami Beach, FL.
authors.forename: Jose
authors.initials: J
authors.lastname: Lutzky
authors.affiliation: Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, MN.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rudraptna
authors.affiliation: Department of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Lee D
authors.initials: LD
authors.lastname: Cranmer
authors.affiliation: Department of Medicine, University of Arizona Medical Center, Tucson, AZ.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Jeter
authors.affiliation: Nebraska Cancer Specialist, Omaha, NE.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Hauke
authors.affiliation: Hematology/Oncology Clinic, Baton Rouge, LA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Miletello
authors.affiliation: Department of Medicine, University of Iowa Hospital and Clinics, Iowa City, IA.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Milhem
authors.affiliation: Blumenthal Cancer Center, Charlotte, NC.
authors.forename: Asim
authors.initials: A
authors.lastname: Amin
authors.affiliation: Division of Hematology and Oncology, St Louis University Department of Internal Medicine, St Louis, MO.
authors.forename: John M
authors.initials: JM
authors.lastname: Richart
authors.affiliation: Department of Medicine, Moffitt Cancer Center, Tampa, FL.
authors.forename: Mayer
authors.initials: M
authors.lastname: Fishman
authors.affiliation: Oncology Specialists, Niles, IL.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Hallmeyer
authors.affiliation: Department of Medicine, University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sapna P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: University of Kansas Medical Center, Kansas City, KS.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Veldhuizen
authors.affiliation: Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Department of Surgery, Columbia University, New York, NY.
authors.forename: Bret
authors.initials: B
authors.lastname: Taback
authors.affiliation: Reiman Cancer Center, Franklin, WI.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Treisman
authors.affiliation: Department of Medicine, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.affiliation: Prometheus Laboratories Inc, San Diego, CA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Perritt
authors.affiliation: Prometheus Laboratories Inc, San Diego, CA.
authors.forename: Hong
authors.initials: H
authors.lastname: Hua
authors.affiliation: Prometheus Laboratories Inc, San Diego, CA.
authors.forename: Tharak B
authors.initials: TB
authors.lastname: Rao
authors.affiliation: Cancer Research Foundation, Chappaqua, NY. Electronic address: jpd4401@aol.com.
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.affiliation: Prometheus Laboratories Inc, San Diego, CA.
authors.forename: Sandra
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authors.lastname: Aung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin
keywords: Anti-VEGF therapy; Cytokine; Kidney cancer; Therapy trends; Toxicity