Effects of cabozantinib on pain and narcotic use in patients with castration-resistant prostate cancer: results from a phase 2 nonrandomized expansion cohort.
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 (100mg or 40mg). 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.
Basch, E; Autio, KA; Smith, MR; Bennett, AV; Weitzman, AL; Scheffold, C; Sweeney, C; Rathkopf, DE; Smith, DC; George, DJ; Higano, CS; Harzstark, AL; Sartor, AO; Gordon, MS; Vogelzang, NJ; de Bono, JS; Haas, NB; Corn, PG; Schimmoller, F; Scher, HI
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