title: Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.
abstract: Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points. Results From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 33% (95% CI, 23 to 44) for cabozantinib versus 12% (95% CI, 5.4 to 21) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%). Conclusion Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Ben L
authors.initials: BL
authors.lastname: Sanford
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Olwen
authors.initials: O
authors.lastname: Hahn
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: M Dror
authors.initials: MD
authors.lastname: Michaelson
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Meghara K
authors.initials: MK
authors.lastname: Walsh
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Thomas
authors.initials: T
authors.lastname: Olencki
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Toni K. Choueiri and Meghara K. Walsh, Dana-Farber Cancer Institute; M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Susan Halabi and Ben L. Sanford, Alliance Statistics and Data Center and Duke University; Daniel J. George, Duke Cancer Institute, Duke University Medical Center, Durham, NC; Olwen Hahn, Alliance Protocol Operations Office, Chicago, IL; Darren R. Feldman and Michael J. Morris, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University Medical Center, Columbus, OH; Joel Picus, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Eric J. Small, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; and Shaker Dakhil, University of Kansas Wichita, Wichita, KS.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D011725:Pyridines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D012307:Risk Factors; D000077210:Sunitinib
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; C558660:cabozantinib; D000077210:Sunitinib