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

BJU Int. 2021 Apr;127(4):435-444. doi: 10.1111/bju.15227. Epub 2020 Oct 23.


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.

Keywords: #PCSM; #ProstateCancer; #uroonc; chemotherapy; combination therapy; metastatic prostate cancer; prostate cancer.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anilides / administration & dosage*
  • Anilides / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Docetaxel / administration & dosage*
  • Docetaxel / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prednisone / administration & dosage*
  • Prednisone / adverse effects
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Treatment Outcome


  • Anilides
  • Antineoplastic Agents
  • Pyridines
  • Docetaxel
  • cabozantinib
  • Prednisone