Cabozantinib Active in Pretreated Metastatic Castration-Resistant Prostate Cancer


Key Points

  • Bone scan response was observed with cabozantinib in 63% of patients, including 73% receiving 100 mg and 45% receiving 40 mg.
  • The higher dose was associated with more frequent dose reduction and discontinuation due to adverse events.

In a phase II expansion study reported in the Journal of Clinical Oncology, Smith et al found that the multikinase inhibitor cabozantinib (Cometriq) showed activity in previously treated metastatic castration-resistant prostate cancer. Cabozantinib targets include VEGFR2 and MET kinases.

Study Details

In the open-label nonrandomized study, 144 patients with bone involvement received either cabozantinib at 100 mg (n = 93) or 40 mg (n = 51) until disease progression or unacceptable toxicity. The primary endpoint was bone scan response, defined as a ≥ 30% reduction in lesion area. Visceral disease was present in 33% of patients. Prior treatments included docetaxel in 100%, abiraterone in 44%, and cabazitaxel in 24%.

Bone Response

Overall, 63% of patients had bone scan response, most by the first measurement at week 6. Median duration of response was 5.2 months (range = 0.03+ to 13.9+ months). The response rate was higher with 100 mg (73% vs45%).

Additional Benefits

Cabozantinib resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55%), as well as improvements in measurable soft-tissue disease (reduction in 80% of 54 evaluable patients), circulating tumor cells (≥ 30% decrease in 82% by week 6 or 12), and bone biomarkers (eg, median reductions of 31%–37% in C-terminal cross-linked telopeptides of type I collagen [CTx] at week 12 and 50%–72% reduction in bone-specific alkaline phosphatase [BSAP] at week 12 or later). Improvements in these measures were similar at both doses. Median overall survival was 10.8 months among all patients, including 12.1 months in the 100-mg group and 9.1 months in the 40-mg group.

Adverse Events

The most common adverse events of any grade with the 100-mg and 40-mg doses were fatigue (83% and 63%), decreased appetite (75% and 45%), nausea (72% and 57%), diarrhea (71% and 43%), weight decrease (45% and 37%), and vomiting (41% and 35%). The most common grade 3 or 4 adverse events were fatigue (27% and 14%), anemia (17% and 6%), hypertension (15% and 12%), nausea (12% and 0%), diarrhea (12% and 2%), and back pain (11% and 10%). Rates of grade ≥ 3 pulmonary embolism were 8% and 18%. Adverse events resulted in dose reduction in 84% and 31% of patients and discontinuation in 25% and 18%. The median average daily doses were 55 mg in the 100-mg group and 36 mg in the 40-mg group.

The investigators concluded: “The evidence suggests that cabozantinib has clinically meaningful activity in [castration-resistant prostate cancer]. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.”

Matthew R. Smith, MD, PhD, of Massachusetts General Hospital, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by awards from the National Institutes of Health, Prostate Cancer Foundation, and Prostate Cancer Clinical Trials Consortium and by Exelixis. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.