title: Effects of cabozantinib on pain and narcotic use in patients with castration-resistant prostate cancer: results from a phase 2 nonrandomized expansion cohort.
abstract: BACKGROUND
  Pain negatively affects quality of life for cancer patients. Preliminary data in metastatic castration-resistant prostate cancer (mCRPC) suggested a benefit of the oral tyrosine kinase inhibitor cabozantinib to pain palliation.
  
  
  OBJECTIVE
  Prospective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC.
  
  
  METHODS
  This was a nonrandomized expansion (NRE) cohort (n=144) of a phase 2 randomized discontinuation trial in docetaxel-refractory mCRPC patients. Pain and interference of symptoms with sleep and general activity were electronically self-reported daily for 7-d intervals at baseline and regularly scheduled throughout the study. Mean per-patient scores were calculated for each interval. Narcotic use was recorded daily during the same intervals.
  
  
  METHODS
  Open-label cabozantinib (100mg or 40mg).
  
  
  METHODS
  The following stringent response definition was used: clinically meaningful pain reduction (≥30% improvement in mean scores from baseline) confirmed at a later interval without concomitant increases in narcotics. Only patients with moderate or severe baseline pain were analyzed.
  
  
  CONCLUSIONS
  Sixty-five patients with moderate or severe baseline pain were evaluable. Of these, 27 (42%) experienced pain palliation according to the stringent response definition. Thirty-seven patients (57%) had clinically meaningful pain relief at two consecutive intervals, reported ≥6 wk apart in the majority. Forty-four patients (68%) had palliation at one or more intervals; 36 (55%) decreased narcotics use during one or more intervals. Clinically meaningful pain reduction was associated with significant (p ≤ 0.001) improvements in sleep quality and general activity. A limitation of this study was its open-label design.
  
  
  CONCLUSIONS
  Cabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients' narcotic use, and improved patient functioning, thus meriting prospective validation in phase 3 studies.
  
  
  RESULTS
  We evaluated the potential of cabozantinib to improve symptoms in patients with metastatic prostate cancer that no longer responds to standard therapies. We saw a promising reduction in pain and reduced need for narcotic painkillers. Larger, well-controlled trials are necessary to confirm these findings.
authors.affiliation: Cancer Outcomes Research Program, Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: Ebasch@med.unc.edu.
authors.forename: Ethan
authors.initials: E
authors.lastname: Basch
authors.affiliation: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weil Cornell Medical College, New York, NY, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Autio
authors.affiliation: Genitourinary Oncology Program, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Cancer Outcomes Research Program, Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Antonia V
authors.initials: AV
authors.lastname: Bennett
authors.affiliation: Clinical Development, Exelixis, Inc., South San Francisco, CA, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Weitzman
authors.affiliation: Clinical Development, Exelixis, Inc., South San Francisco, CA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Scheffold
authors.affiliation: Genitourinary Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sweeney
authors.affiliation: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.affiliation: Genitourinary Medical Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA.
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Urologic Surgery and Oncology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Harzstark
authors.affiliation: Tulane Cancer Center, Tulane University, New Orleans, LA, USA.
authors.forename: A Oliver
authors.initials: AO
authors.lastname: Sartor
authors.affiliation: Pinnacle Oncology Hematology, Scottsdale, AZ, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.affiliation: Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Drug Development Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Haas
authors.affiliation: Department of Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.affiliation: Clinical Development, Exelixis, Inc., South San Francisco, CA, USA.
authors.forename: Frauke
authors.initials: F
authors.lastname: Schimmoller
authors.affiliation: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weil Cornell Medical College, New York, NY, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D010166:Palliative Care; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D014481:United States
chemical_list: D000701:Analgesics, Opioid; D000813:Anilides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib
keywords: Pain control; Patient-reported outcomes; Phase 2 trial; Quality of life; Tyrosine kinase inhibitor; mCRPC