title: A systematic review of the efficacy and safety experience reported for sorafenib in advanced renal cell carcinoma (RCC) in the post-approval setting.
abstract: BACKGROUND
  Sorafenib was FDA approved in 2005 for treatment of renal cell carcinoma (RCC) based on the results of the pivotal phase 3 clinical trial, TARGET (Treatment Approaches in Renal Cancer Global Evaluation Trial). Since that time, numerous clinical studies have been undertaken that substantially broaden our knowledge of the use of sorafenib for this indication.
  
  
  METHODS
  We systematically reviewed PubMed, Web of Science, Embase, Cochrane Library, and www.clinicaltrials.gov for prospective clinical studies using single agent sorafenib in RCC and published since 2005. Primary endpoints of interest were progression-free survival (PFS) and safety. PROSPERO International prospective register of systematic reviews #CRD42014010765.
  
  
  RESULTS
  We identified 30 studies in which 2182 patients were treated with sorafenib, including 1575 patients who participated in randomized controlled phase 3 trials. In these trials, sorafenib was administered as first-, second- or third-line treatment. Heterogeneity among trial designs and reporting of data precluded statistical comparisons among trials or with TARGET. The PFS appeared shorter in second- vs. first-line treatment, consistent with the more advanced tumor status in the second-line setting. In some trials, incidences of grade 3/4 hypertension or hand-foot skin reaction (HFSR) were more than double that seen in TARGET (4% and 6%, respectively). These variances may be attributable to increased recognition of HFSR, or potentially differences in dose adjustments, that could be consequences of increased familiarity with sorafenib usage. Several small studies enrolled exclusively Asian patients. These studies reported notably longer PFS than was observed in TARGET. However, no obvious corresponding differences in disease control rate and overall survival were seen.
  
  
  CONCLUSIONS
  Collectively, more recent experiences using sorafenib in RCC are consistent with results reported for TARGET with no marked changes of response endpoints or new safety signals observed.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors.forename: Mayer N
authors.initials: MN
authors.lastname: Fishman
authors.affiliation: Blue Ocean Pharma LLC, Annandale, New Jersey, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Tomshine
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Fulp
authors.affiliation: Blue Ocean Pharma LLC, Annandale, New Jersey, United States of America.
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Foreman
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D012449:Safety; D000077157:Sorafenib
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
references.citation: BJU Int. 2011 Dec;108(11):1813-9
references.pmid: 21481133
references.citation: Cancer. 2010 Jan 1;116(1):57-65
references.pmid: 19862815
references.citation: Lancet Oncol. 2013 Dec;14(13):1287-94
references.pmid: 24206640
references.citation: Cancer. 2012 Dec 15;118(24):6152-61
references.pmid: 22692704
references.citation: Oncol Lett. 2012 Apr 1;3(4):935-939
references.pmid: 22741022
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1280-9
references.pmid: 19171708
references.citation: J Clin Oncol. 2013 Oct 20;31(30):3791-9
references.pmid: 24019545
references.citation: BMC Cancer. 2009 Jul 21;9:249
references.pmid: 19622166
references.citation: Oncology. 2010;78(5-6):340-7
references.pmid: 20733337
references.citation: Asia Pac J Clin Oncol. 2014 Mar;10(1):60-5
references.pmid: 24152417
references.citation: Br J Cancer. 2013 Apr 30;108(8):1571-8
references.pmid: 23579211
references.citation: Lancet Oncol. 2013 May;14(6):552-62
references.pmid: 23598172
references.citation: J Clin Oncol. 2014 Mar 10;32(8):760-7
references.pmid: 24297950
references.citation: Ann Oncol. 2008 Sep;19 Suppl 8:viii21-287
references.pmid: 18790885
references.citation: Ann Oncol. 2011 Aug;22(8):1812-23
references.pmid: 21324953
references.citation: Ann Oncol. 2012 Jan;23(1):46-52
references.pmid: 21464158
references.citation: Cancer. 2010 Dec 1;116(23):5383-90
references.pmid: 20806321
references.citation: Oncology. 2008;74(3-4):216-22
references.pmid: 18714170
references.citation: Future Oncol. 2012 Aug;8(8):1051-7
references.pmid: 22894676
references.citation: Jpn J Clin Oncol. 2007 Oct;37(10):755-62
references.pmid: 17951335
references.citation: Lancet Oncol. 2014 Mar;15(3):286-96
references.pmid: 24556040
references.citation: Jpn J Clin Oncol. 2013 Jun;43(6):616-28
references.pmid: 23630366
references.citation: Clin Transl Oncol. 2013 Sep;15(9):698-704
references.pmid: 23359179
references.citation: J Clin Oncol. 2006 Jun 1;24(16):2505-12
references.pmid: 16636341
references.citation: Cancer. 2010 Mar 1;116(5):1272-80
references.pmid: 20082451
references.citation: Br J Cancer. 2015 Jan 6;112(1):14-9
references.pmid: 25375270
references.citation: Lancet. 2011 Dec 3;378(9807):1931-9
references.pmid: 22056247
references.citation: Oncology. 2007;73(3-4):204-9
references.pmid: 18418013
references.citation: Br J Cancer. 2011 Apr 12;104(8):1256-61
references.pmid: 21448165
references.citation: Ann Oncol. 2013 Dec;24(12):2967-71
references.pmid: 24063860
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530