Another kinase inhibitor shows only “modest” activity in men with mCRPC

A relatively small Phase II trial, carried out in France and Germany, has suggested that a new kinase inhibitor called nintedanib has only “modest” activity in the treatment of post-chemotherapy, metastatic, castration-resistant prostate cancer (mCRPC).

Droz et al. conducted an open-label (i.e., non-blinded), Phase II trial to evaluate the efficacy and safety of two doses of nintedanib in patients with mCRPC who had progressive disease after treatment with docetaxel-based chemotherapy. Nintedanib is a triple angiokinase inhibitor that supposedly targets vascular endothelial growth factor (VEGF), fibroblast growth factor FGF), and platelet-derived growth factor (PDGF) signaling. The patients were randomized to receive one or other of two treatments until disease progression or adverse events led to discontinuation of treatment:

  • Group A: Nintedanib 150 mg b.i.d for up to 6 months (n = 40)
  • Group B: Nintedanib 250 mg b.i.d for up to 6 months (n = 41)

The primary endpoint was  a confirmed decline in PSA level of ≥ 20 percent from baseline (which is not exactly a high bar to cross with regard to efficacy).

Here are the core study findings:

  • For patients in Group A,
    • 0/32 patients (0 percent) met the primary endpoint after 6 months.
    • Average (median) progression-free survival was 73.5 days.
  • For patients in Group B,
    • 4/36 patients (11.1 percent) showed a PSA reduction of ≥ 20 percent after 6 months.
    • 2/36 patients (5.6 percent) showed a PSA reduction of ≥ 50 percent after 6 months.
    • Compared to the rate of PSA increase before treatment, the rate of PSA increase was significantly decelerated on treatment with nintedanib.
    • Average (median) progression-free survival was 76.0 days.
  • Adverse events associated with treatment included gastrointestinal disorders, asthenia, hypertension, and reversible elevations in transaminase levels.
  • The incidence of serious, drug-related adverse events (presumed to mean grades 3 and 4) was
    • 20.0 percent among patients in Group A (with no deaths)
    • 24.4 percent among patients in Group B (again with no deaths)).
  • The primary study endpoint was not met.

It seems unlikely that the developer will continue to pursue the development of nintedanib in the treatment of advanced prostate cancer given the results of this study and the failure of other forms of kinase inhibitor to show significant clinical impact in the treatment of mCRPC.

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