Cabozantinib improves quality of life in men with CPRC and mCRPC

Just over a year ago a poster presented by Basch et al. at an international conference reported data on 67 men with metastatic, castration-resistant prostate cancer (mCRPC) who were treated in a Phase II clinical trial with a daily dose of cabozantinib 100 mg after prior treatment with docetaxel-based chemotherapy. That poster showed a significant reduction in risk for bone-related pain and other improvements in quality of life among the men treated with cabozantinib.

A new paper by Smith et al., just published in the Journal of Clinical Oncology, provides follow-up data on that original report, with data on the treatment of 171 patients with mCRPC or non-metastatic CRPC.

Patients initially received 100 mg of cabozantinib daily. Those shown to have stable disease at 12 weeks were then (initially) randomized to continue on cabozantinib or to receive a placebo instead. However, random assignment was stopped early because of the observed activity of cabozantinib and all 171 patients continued to receive 100 mg of cabozantinib daily.

Of the 171 patients enrolled in the trial,

  • 87 percent had evident bone metastases (i.e., mCRPC).
  • 46 percent had already received chemotherapy (almost all with docetaxel-based therapy).
  • 39 percent had received previous and ongoing bisphosphonate treatment.

Smith et al. now report that:

  • 72 percent of patients had regression in soft tissue lesions.
  • 68 percent of evaluable patients had improvement on bone scan.
  • 12 percent of patients had complete complete resolution of their disease on bone scan.
  • The objective response rate (ORR) at 12 weeks was 5 percent, with stable disease in 75 percent of patients.
  • Just 31 patients with stable disease at week 12 were initially randomized to continued cabozantinib or to a placebo, and among those 31 patients,
    • Median progression-free survival (PFS) was 23.9 weeks for the patients taking cabozantinib.
    • Median PFS was only 5.9 weeks for the patients taking the placebo.
  • On retrospective review,
    • Bone pain improved in 67 percent of evaluable patients
    • There was a decrease in narcotic use in 56 percent of evaluable patients.
  • The most common grade 3 adverse events were fatigue (16 percent), hypertension (12 percent), and hand-foot syndrome (8 percent).

The authors conclude that, “Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.”

As we have already reported, the developers of cabozantinib are currently conducting two Phase III, randomized, double-blind trials to evaluate the effects of cabozantinib in men with mCRPC with the goal of obtaining approval of this drug in the treatment of late stage prostate cancer. We have also noted previously that cabozantinib is associated with a number of serious potential adverse effects in addition to the common side effects listed above.

In a Medscape report on the data from this paper, the lead author, Dr. David Smith of the University of Michigan is quoted as stating that, “Cabozantinib should not be used for CRPC outside of clinical trials at this point, but the data should prompt referrals for clinical trials” (e.g., the phase III trials referred to above and other trials listed on

He also noted that, “Dosing is still being assessed and the side-effect profile requires that patients be closely monitored to limit major toxicities. I would not recommend off-label use at this time.”

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