title: A phase 2 trial of sunitinib in patients with advanced non-clear cell renal cell carcinoma.
abstract: BACKGROUND
  Sunitinib is a standard-of-care treatment in advanced clear cell renal cell carcinoma (ccRCC). Retrospective and expanded access data suggest sunitinib has activity in advanced non-clear cell renal cell carcinoma (nccRCC).
  
  
  OBJECTIVE
  To prospectively determine the clinical efficacy and safety of sunitinib in patients with advanced nccRCC.
  
  
  METHODS
  This is a single-arm phase 2 trial with a two-stage design. Eligibility criteria included pathologically confirmed nccRCC or ccRCC with ≥ 20% sarcomatoid histology, performance status 0-2, measurable disease, a maximum of two prior systemic therapies, and no prior treatment with tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptors.
  
  
  METHODS
  Patients received sunitinib 50mg daily on a 4-wk on, 2-wk off schedule.
  
  
  METHODS
  Primary end points were objective response rate (ORR) and progression-free survival (PFS). Secondary end points were safety and overall survival (OS).
  
  
  CONCLUSIONS
  Fifty-seven patients were eligible (nccRCC histology: papillary, 27; chromophobe, 5; unclassified, 8; collecting duct or medullary carcinoma, 6; sarcomatoid, 7; and others, 4). Median PFS for 55 evaluable patients was 2.7 mo (95% confidence interval [CI], 1.4-5.4). Two patients with chromophobe and one patient with unclassified histology had a confirmed partial response (5% ORR). Median PFS for patients with papillary histology was 1.6 mo (95% CI, 1.4-5.4). Median PFS for patients with chromophobe histology was 12.7 mo (95% CI, 8.5-NA). Median OS for all patients was 16.8 mo (95% CI, 10.7-26.3). Treatment-emergent adverse events were consistent with sunitinib's mechanism of action. The nonrandomized design and small number of patients are limitations of this study.
  
  
  CONCLUSIONS
  The differential response of chromophobe histology to sunitinib suggests a therapeutically relevant biological heterogeneity exists within nccRCC. The low ORR and short PFS with sunitinib in the other nccRCC subtypes underscore the need to enroll patients with these diverse tumors in clinical trials.
authors: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ntannir@mdanderson.org
authors: Nizar M
authors: NM
authors: Tannir
authors: Elizabeth
authors: E
authors: Plimack
authors: Chaan
authors: C
authors: Ng
authors: Pheroze
authors: P
authors: Tamboli
authors: Nebiyou B
authors: NB
authors: Bekele
authors: Lianchun
authors: L
authors: Xiao
authors: Lisa
authors: L
authors: Smith
authors: Zita
authors: Z
authors: Lim
authors: Lance
authors: L
authors: Pagliaro
authors: John
authors: J
authors: Araujo
authors: Ana
authors: A
authors: Aparicio
authors: Surena
authors: S
authors: Matin
authors: Christopher G
authors: CG
authors: Wood
authors: Eric
authors: E
authors: Jonasch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib