title: Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category.
abstract: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response.
  
  
  
  To assess outcomes of 2L according to type of therapy and change in IMDC prognostic category.
  
  
  
  We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology.
  
  
  
  All included patients received targeted therapy for mRCC.
  
  
  
  Overall survival (OS), time to treatment failure, and response to 2L were analyzed using Cox or logistic regression.
  
  
  
  At start of 2L, 60% of patients remained in the same prognostic category; 9.0% improved (3% I → F; 6% P → I); 31% deteriorated (15% F → I or P; 16% I → P). Patients with the same or better IMDC prognostic category had a longer time to treatment failure if they remained on VEGFi compared to those who switched to mTORi (adjusted hazard ratio [AHR] ranging from 0.33 to 0.78, adjusted p<0.05). Patients who deteriorated from F to I appeared more likely to benefit from switching to mTORi (median OS 16.5 mo, 95% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03).
  
  
  
  Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy.
  
  
  
  The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma.
authors: Monash University and Eastern Health, Box Hill. Victoria, Australia. Electronic address: ian.davis@monash.edu.
authors: Ian D
authors: ID
authors: Davis
authors: Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: Wanling
authors: W
authors: Xie
authors: Monash University and Eastern Health, Box Hill. Victoria, Australia.
authors: Carmel
authors: C
authors: Pezaro
authors: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Frede
authors: F
authors: Donskov
authors: Tom Baker Cancer Centre, Calgary, AB, Canada.
authors: J Connor
authors: JC
authors: Wells
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors: Neeraj
authors: N
authors: Agarwal
authors: Stanford University Medical Center, Stanford, CA, USA.
authors: Sandy
authors: S
authors: Srinivas
authors: Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Yuasa
authors: Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
authors: Benoit
authors: B
authors: Beuselinck
authors: Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
authors: Lori A
authors: LA
authors: Wood
authors: London Regional Cancer Centre, London, ON, Canada.
authors: D Scott
authors: DS
authors: Ernst
authors: National Cancer Centre Singapore, Singapore.
authors: Ravindran
authors: R
authors: Kanesvaran
authors: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
authors: Jennifer J
authors: JJ
authors: Knox
authors: UCLA Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Allan
authors: A
authors: Pantuck
authors: The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors: Sadia
authors: S
authors: Saleem
authors: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors: Ajjai
authors: A
authors: Alva
authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors: Brian I
authors: BI
authors: Rini
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors: Jae-Lyun
authors: JL
authors: Lee
authors: Dana Farber Cancer Institute, Boston, MA, USA.
authors: Toni K
authors: TK
authors: Choueiri
authors: Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada.
authors: Daniel Y C
authors: DYC
authors: Heng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D057915:Drug Substitution; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D016017:Odds Ratio; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases
keywords: Carcinoma; Database; Follow-up studies; Logistic models; Renal cell