title: First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC.
abstract: BACKGROUND
  Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.
  
  
  METHODS
  Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.
  
  
  RESULTS
  In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.
  
  
  CONCLUSIONS
  Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.
authors.affiliation: Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada.
authors.forename: J J
authors.initials: JJ
authors.lastname: Ko
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Rini
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: J-L
authors.initials: JL
authors.lastname: Lee
authors.affiliation: 1] Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada [2] Department of Urology, Universitätsmedizin Greifswald, Greifswald, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kroeger
authors.affiliation: Division of Oncology, Stanford Medical Center, Stanford, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Division of Oncology, Stanford Cancer Institute, Stanford School of Medicine, Stanford, California, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Harshman
authors.affiliation: Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Bjarnason
authors.affiliation: London Health Sciences Center, London, Ontario, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: MacKenzie
authors.affiliation: Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Wood
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
authors.forename: U N
authors.initials: UN
authors.lastname: Vaishampayan
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
authors.forename: N
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: City of Hope Comprehensive Cancer Center, Medical Oncology & Experimental Therapeutics, Duarte, California, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: National Cancer Center, Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
authors.forename: M-H
authors.initials: MH
authors.lastname: Tan
authors.affiliation: Yonsei University Hospital, Seoul, South Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Department of Urology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yuasa
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Alexandra Peripheral General Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Bamias
authors.affiliation: Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada.
authors.forename: D Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases