Effects of Cabozantinib on Pain and Narcotic Use in Patients with Castration-resistant Prostate Cancer: Results from a Phase 2 Nonrandomized Expansion Cohort

• Published in: European urology Vol. 67; no. 2; pp. 310 - 318
• Main Authors: Basch, Ethan, Autio, Karen A, Smith, Matthew R, Bennett, Antonia V, Weitzman, Aaron L, Scheffold, Christian, Sweeney, Christopher, Rathkopf, Dana E, Smith, David C, George, Daniel J, Higano, Celestia S, Harzstark, Andrea L, Sartor, A. Oliver, Gordon, Michael S, Vogelzang, Nicholas J, de Bono, Johann S, Haas, Naomi B, Corn, Paul G, Schimmoller, Frauke, Scher, Howard I
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.02.2015
• Subjects: Aged; Analgesics, Opioid - therapeutic use; Anilides - therapeutic use; Antineoplastic Agents - therapeutic use; Humans; Male; mCRPC; Middle Aged; Pain - diagnosis; Pain - drug therapy; Pain - etiology; Pain control; Pain Measurement; Palliative Care; Patient-reported outcomes; Phase 2 trial; Prospective Studies; Prostatic Neoplasms, Castration-Resistant - complications; Prostatic Neoplasms, Castration-Resistant - diagnosis; Prostatic Neoplasms, Castration-Resistant - drug therapy; Protein Kinase Inhibitors - therapeutic use; Pyridines - therapeutic use; Quality of life; Severity of Illness Index; Time Factors; Treatment Outcome; Tyrosine kinase inhibitor; United Kingdom; United States; Urology; mCRPC; Phase 2 trial; Patient-reported outcomes; Pain control; Tyrosine kinase inhibitor; Quality of life
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2014.02.013

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. Design, setting, and participants 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. Intervention Open-label cabozantinib (100 mg or 40 mg). Outcome measurements and statistical analysis 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. Results and limitations 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. Patient summary 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.