title: Long-term outcomes of tyrosine kinase inhibitor discontinuation in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  The purpose of the current study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who interrupted vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy.
  
  
  METHODS
  A retrospective analysis of medical records was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n = 505). Patients who achieved stable disease (SD) or a better response under TKI and later discontinued TKI treatment for any reason with the exception of disease progression were included in the analysis.
  
  
  RESULTS
  We identified 32 patients (sunitinib = 20, sorafenib = 7, and pazopanib = 5). The responses to VEGFR-TKIs were complete response (CR, n = 4), partial response (PR, n = 11), SD (n = 15), and controlled but nonmeasurable response (n = 2). Median time to TKI discontinuation from the initiation of VEGFR-TKI therapy was 16.6 months (95 % CI 12.8-20.3), and the main cause of VEGFR-TKI discontinuation was toxicity (n = 19, 59.4 %). At the time of analysis, 16 patients had disease progression and one patient died. With a median follow-up duration of 51.7 months (range 11.5-87.6), median progression-free survival (PFS) after TKI discontinuation was 20.2 months (95 % CI 6.4-34.0). In multivariate analysis, the duration of TKI therapy (<1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (p = 0.045). Among 11 patients who were retreated with the same TKI, two patients (18.2 %) achieved PR and nine achieved SD (81.8 %).
  
  
  CONCLUSIONS
  VEGFR-TKI could be interrupted at least temporarily when clinically warranted in patients with mRCC sufficiently controlled by TKIs.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.|Division of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong-Hoe
authors.initials: DH
authors.lastname: Koo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.|Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Inkeun
authors.initials: I
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dalsan
authors.initials: D
authors.lastname: You
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: In-Gab
authors.initials: IG
authors.lastname: Jeong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Cheryn
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Bumsik
authors.initials: B
authors.lastname: Hong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Hong
authors.affiliation: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hanjong
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. jaelyun@amc.seoul.kr.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D000077157:Sorafenib; D013449:Sulfonamides / Q000494:pharmacology*; D000077210:Sunitinib; D013997:Time Factors; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib
keywords: Observation; Renal cell carcinoma; Treatment interruption; VEGFR–TKIs