Cabozantinib versus mitoxantrone-prednisone in symptomatic metastatic castration-resistant prostate cancer: A randomized phase 3 trial with a primary pain endpoint Journal Article
| Authors: | Basch, E. M.; Scholz, M.; de Bono, J. S.; Vogelzang, N.; de Souza, P.; Marx, G.; Vaishampayan, U.; George, S.; Schwarz, J. K.; Antonarakis, E. S.; O'Sullivan, J. M.; Kalebasty, A. R.; Chi, K. N.; Dreicer, R.; Hutson, T. E.; Dueck, A. C.; Bennett, A. V.; Dayan, E.; Mangeshkar, M.; Holland, J.; Weitzman, A. L.; Scher, H. I. |
| Article Title: | Cabozantinib versus mitoxantrone-prednisone in symptomatic metastatic castration-resistant prostate cancer: A randomized phase 3 trial with a primary pain endpoint |
| Abstract: | Background: Bone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with debilitating pain and functional compromise. Objective: To compare pain palliation as the primary endpoint for cabozantinib versus mitoxantrone-prednisone in men with mCRPC and symptomatic bone metastases using patient-reported outcome measures. Design, setting, and participants: A randomized, double-blind phase 3 trial (COMET-2; NCT01522443) in men with mCRPC and narcotic-dependent pain from bone metastases who had progressed after treatment with docetaxel and either abiraterone or enzalutamide. Intervention: Cabozantinib 60 mg once daily orally versus mitoxantrone 12 mg/m 2 every 3 wk plus prednisone 5 mg twice daily orally. Outcome measurements and statistical analysis: The primary endpoint was pain response at week 6 confirmed at week 12 (≥30% decrease from baseline in patient-reported average daily worst pain score via the Brief Pain Inventory without increased narcotic use). The planned sample size was 246 to achieve ≥90% power. Results and limitations: Enrollment was terminated early because cabozantinib did not demonstrate a survival benefit in the companion COMET-1 trial. At study closure, 119 participants were randomized (cabozantinib: N = 61; mitoxantrone-prednisone: N = 58). Complete pain and narcotic use data were available at baseline, week 6, and week 12 for 73/106 (69%) patients. There was no significant difference in the pain response with cabozantinib versus mitoxantrone-prednisone: the proportions of responders were 15% versus 17%, a −2% difference (95% confidence interval: −16% to 11%, p = 0.8). Barriers to accrual included pretreatment requirements for a washout period of prior anticancer therapy and a narcotic optimization period to maximize analgesic dosing. Conclusions: Cabozantinib treatment did not demonstrate better pain palliation than mitoxantrone-prednisone in heavily pretreated patients with mCRPC and symptomatic bone metastases. Future pain-palliation trials should incorporate briefer timelines from enrollment to treatment initiation. Patient summary: Cabozantinib was not better than mitoxantrone-prednisone for pain relief in patients with castration-resistant prostate cancer and debilitating pain from bone metastases. Control of debilitating pain is an unmet need for men with metastatic castration-resistant prostate cancer (mCRPC). This phase 3 trial failed to show an improved pain response for cabozantinib compared with mitoxantrone-prednisone in patients with previously treated, symptomatic mCRPC. © 2018 The Authors |
| Keywords: | clinical trial; prostate cancer; pain assessment; cabozantinib |
| Journal Title: | European Urology |
| Volume: | 75 |
| Issue: | 6 |
| ISSN: | 0302-2838 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2019-06-01 |
| Start Page: | 929 |
| End Page: | 937 |
| Language: | English |
| DOI: | 10.1016/j.eururo.2018.11.033 |
| PROVIDER: | scopus |
| PUBMED: | 30528222 |
| PMCID: | PMC6876845 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 June 2019 -- Source: Scopus |
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