Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer

Ravi A. Madan, Fatima H. Karzai, Munjid Al Harthy, Daniel P. Petrylak, Joseph W. Kim, Philip M. Arlen, Inger Rosner, Marc R. Theoret, Lisa Cordes, Marijo Bilusic, Cody J. Peer, Nancy A. Dawson, Anna Couvillon, Amy Hankin, Moniquea Williams, Guin Chun, Helen Owens, Jennifer L. Marte, Min Jung Lee, Yusuke TomitaAkira Yuno, Jane B. Trepel, Sunmin Lee, Seth M. Steinberg, James L. Gulley, William D. Figg, William L. Dahut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Objective: To evaluate the safety and efficacy of cabozantinib combined with docetaxel. Patients and Methods: This was a phase 1/2 multicentre study in patients with metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (75 mg/m2 every 3 weeks with daily prednisone 10 mg) was combined with escalating doses of daily cabozantinib (20, 40 and 60 mg). Based on the results of the phase 1 study, the investigation was expanded into a randomized study of docetaxel with prednisone (hereafter 'docetaxel/prednisone') plus the maximum tolerated dose (MTD) of cabozantinib compared with docetaxel/prednisone alone. Results: A total of 44 men with mCRPC were enrolled in this phase 1/2 trial. An MTD of 40 mg cabozantinib plus docetaxel/prednisone was determined. Dose-limiting toxicities were neutropenic fever and palmar-plantar erythrodysesthesia, and there was one death attributable to a thromboembolic event. In addition, grade 3 or 4 myelosuppression, hypophosphataemia and neuropathy were seen in three or more patients. In the phase 1 study, the median time to progression (TTP) and overall survival (OS) time were 13.6 and 16.3 months, respectively. In the phase 2 study, which was terminated early because of poor accrual, the median TTP and OS favoured the combination (n = 13) compared to docetaxel/prednisone alone (n = 12; 21.0 vs 6.6 months; P = 0.035 and 23.8 vs 15.6 months; P = 0.072, respectively). Conclusion: Despite the limited number of patients in this study, preliminary data suggest that cabozantinib can be safely added to docetaxel/prednisone with possible enhanced efficacy.

Original languageEnglish
Pages (from-to)435-444
Number of pages10
JournalBJU International
Issue number4
StatePublished - Apr 2021
Externally publishedYes


  • #PCSM
  • #ProstateCancer
  • #uroonc
  • chemotherapy
  • combination therapy
  • metastatic prostate cancer
  • prostate cancer


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