title: Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials.
abstract: BACKGROUND
  Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown.
  
  
  METHODS
  mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10(3)/uL, or neutrophil count <1500/mm(3).
  
  
  RESULTS
  Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001).
  
  
  CONCLUSIONS
  The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.
authors.affiliation: Tom Baker Cancer Center, Calgary, AB, Canada.
authors.forename: D Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: B I
authors.initials: BI
authors.lastname: Rini
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Yuasa
authors.forename: S K
authors.initials: SK
authors.lastname: Pal
authors.forename: S
authors.initials: S
authors.lastname: Srinivas
authors.forename: G A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: J J
authors.initials: JJ
authors.lastname: Knox
authors.forename: M
authors.initials: M
authors.lastname: Mackenzie
authors.forename: U N
authors.initials: UN
authors.lastname: Vaishampayan
authors.forename: M H
authors.initials: MH
authors.lastname: Tan
authors.forename: S Y
authors.initials: SY
authors.lastname: Rha
authors.forename: F
authors.initials: F
authors.lastname: Donskov
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.forename: C
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: S
authors.initials: S
authors.lastname: North
authors.forename: L A
authors.initials: LA
authors.lastname: Wood
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D004608:Eligibility Determination; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D000077210:Sunitinib
keywords: clinical trials; ineligible; metastatic renal cell cancer; outcomes