Tasquinimod in treatment of patients with metastatic CRPC

Looking quickly through the abstracts of presentations on investigational  therapies to be presented at the annual meeting of the American Society for Clinical Oncology (ASCO), starting on June 4 in Chicago, one particular paper stood out — a Phase II trial of tasquinimod.

Tasquinimod is an orally administered, investigational drug that has previously been shown to have both anti-angiogenic properties and anti-tumor activity in prostate cancer models. Earlier (Phase I) clinical trials of tasquinimod have shown that is well tolerated and that it may delay progression of prostate cancer.

Pili et al. recruited 206 patients, all of whom had metastatic, castration-resistant prostate cancer (mCRPC). These patients were randomly assigned (on a 2:1 basis) to either receive tasquinimod or a placebo. The tasquinimod patients were started at an initial dose of 0.25 mg once daily, and their dose was increased gradually to 1.0 mg/day over 4 weeks.

The results of the study, as presented in the on-line abstract, are as follows:

  • 200 patients were evaluable for efficacy and safety (133 tasquinimod patients and 67 placebo patients).
  • The median age of these  200 patients was 72.5 years.
  • Median baseline characteristics of patients in the two arms of the trial were generally very similar, but  the media alkaline phosphatase level and the median PSA level was noticeably higher for patients in the tasquinimod group.
  • At 6 months after initiation of treatment, 57 percent of patients in the tasquinimod group were progression-free as compared to 33 percent of patients in the placebo group (p=0.0001)
  • Median progression-free survival was 24.7 weeks for patients in the tasquinimod group as compared to 12.9 weeks in the placebo group. In other words tasquinimod nearly doubled progression-free survival compared to a placebo in this group of patients.
  • Side effects were manageable, but significant:
    • Serious vascular events were more common among tasquinimod patients, and included myocardial infarction, heart failure or stroke (3 percent vs 0  percent) and deep vein thrombosis (4  percent vs 0  percent).
    • Common adverse events occurring more frequently in patients receiving tasquinimod included gastrointestinal disorders, fatigue, and musculoskeletal pains.
    • Grade 3/4 adverse events were reported in 38 percent of patients on tasquinimod compared to 10 percent of patients receiving the placebo. 

It is clear that tasquinimod was able to delay progression of prostate cancer and to improve progression-free survival in patients with mCRPC compared to a placebo. The abstract states that a phase III study is planned, but there is no information about such a trial on the ClinicalTrials.gov web site as of today.

In addition, since this abstract was presumably submitted for presentation several months ago, it will be interesting to see if updated information suggests any improvements in the comparative outcomes for patients receiving the active drug.

The question that will need to be addressed next is whether tasquinimod can still be compared to docetaxel + prednisone in a Phase III clinical trial in mCRPC patients, whether it should be compared to Provenge in mCRPC patients with minimal symptoms of advanced disease, or whether it can still be compared to a placebo in CRPC patients who have relapsed after treatment with docetaxel. (It should be remembered that cabazitaxel has already reported a survival benefit of 2+ months compared to a placebo in patients who have relapsed after treatment with docetaxel in a randomized Phase III clinical trial, but cabazitaxel has yet to be approved by the US FDA.)

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