• Ethan Basch, Karen A Autio, Matthew R Smith, Antonia V Bennett, Aaron L Weitzman, Christian Scheffold, Christopher Sweeney, Dana E Rathkopf, David C Smith, Daniel J George, Celestia S Higano, Andrea L Harzstark, A Oliver Sartor, Michael S Gordon, Nicholas J Vogelzang, Johann S de Bono, Naomi B Haas, Paul G Corn, Frauke Schimmoller, and Howard I Scher.
• Cancer Outcomes Research Program, Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: Ebasch@med.unc.edu.
• Eur. Urol. 2015 Feb 1; 67 (2): 310-8.

BackgroundPain 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.ObjectiveProspective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC.Design, Setting, And ParticipantsThis 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.InterventionOpen-label cabozantinib (100mg or 40mg).Outcome Measurements And Statistical AnalysisThe 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.Results And LimitationsSixty-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.ConclusionsCabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients' narcotic use, and improved patient functioning, thus meriting prospective validation in phase 3 studies.Patient SummaryWe 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.Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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