title: Sequential targeted therapy after pazopanib therapy in patients with metastatic renal cell cancer: efficacy and toxicity.
abstract: BACKGROUND
  Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy.
  
  
  METHODS
  Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented.
  
  
  RESULTS
  Subsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti-VEGF- and everolimus-treated patients, respectively (P = .021).
  
  
  CONCLUSIONS
  In this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Hospital del Mar, Barcelona, Spain. Electronic address: joaquim_bellmunt@dfci.harvard.edu.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Pons
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Foreshew
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: St Bartholomew's Hospital, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: IRCCS San Matteo University Hospital Fundantion, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Istituto Toscano Tumori, Arezzo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lampron
authors.affiliation: San Camilo and Forlanini Hospitals, Rome, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerbone
authors.affiliation: San Camilo and Forlanini Hospitals, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: GU Center of Excellence Texas Oncology, Dallas, TX.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.affiliation: GU Center of Excellence Texas Oncology, Dallas, TX.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; C401859:temsirolimus; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus
keywords: Pazopanib; Renal cell carcinoma; Sequential therapy; VEGF-targeted therapy; mTOR inhibitor