title: Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma.
abstract: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason for discontinuation of first-line (1L) therapy is unknown.
  
  
  
  Patients from 15 International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) centers who started 2L targeted therapy were included and the reason for discontinuation of 1L therapy retrospectively collected. Treatment outcomes of 2L, including response, time to treatment failure, and overall survival (OS) were assessed.
  
  
  
  In total, 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT because of disease progression, and 208 patients (19%) because of toxicity. The reason for discontinuation of 1L therapy did not differ according to IMDC risk group. Compared with patients who stopped 1L VEGF-TT because of disease progression, patients who stopped because of toxicity had greater clinical benefit (nonprogressive disease as best response) in 2L treatment (68% vs. 56%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.07-2.35; P = .023) and longer OS (17.4 vs. 11.2 months; adjusted hazard ratio, 0.69; 95% CI, 0.56-0.84; P = .0002) adjusted for type of therapy, time to initiation of 2L treatment, IMDC risk group, and number of metastases at initiation of 2L treatment.
  
  
  
  mRCC patients who discontinue 1L VEGF-TT because of toxicity have better outcomes with 2L therapy than patients who stop therapy because of disease progression. These findings should be taken into consideration when designing clinical trials for 2L therapies in mRCC.
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: De Velasco
authors.affiliation: Deparment of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA.
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beuselinck
authors.affiliation: Division of Oncology, Stanford Medical Center, Stanford, CA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Division of Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Department of Oncology, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jae Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Hematology-Oncology Division, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: James
authors.initials: J
authors.lastname: Brugarolas
authors.affiliation: Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Wood
authors.affiliation: Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: British Columbia Cancer Agency-Vancouver Cancer Center, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Reuben
authors.initials: R
authors.lastname: Broom
authors.affiliation: Hematology-Oncology Division, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Haru
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA.
authors.forename: Marina D
authors.initials: MD
authors.lastname: Kaymakcalan
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Daniel Y C
authors.initials: DYC
authors.lastname: Heng
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA. Electronic address: Toni_Choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A
keywords: Discontinuation therapy; Early discontinuation; IMDC; Systemic treatment; VEGF-TT-intolerant patients