Data from the long-term follow-up of a Phase II trial of tasquinimod in mCRPC

More than 3 years ago now, we reported that Pili et al. presented data from a Phase II trial of tasquinimod showing progression-free and overall survival benefits compared to a placebo in the management of men with metastatic, castration-resistant prostate cancer (mCRPC). In February 2011 we reported an update to these data by Armstrong et al.

A newly published paper by Armstrong et al. now offers data from roughly 3 years of follow-up of the men in this trial. Additional information about this study is also available on the Medscape Oncology web site.

As a reminder, tasquinimod is an oral, immunomodulatory, anti-angiogenic, anti-metastatic agent drug being developed by a Swedish company called Active Biotech. With regard to its potential in the management of prostate cancer, it has been tested only in men with mCRPC. A follow-up Phase III clinical trial is fully enrolled, and the drug is also being tested in combination with cabazitaxel (the CATCH trial) and as maintenance therapy in men with mCRPC who are not progressing after docetaxel-based chemotherapy.

In their most recent paper, Armstrong et al. report as follows:

  • The original Phase II trial evaluated 201 patients with mCRPC who had been randomized (2:1) to either tasquinimod (n = 134) or a placebo (n = 67).
  • 41/67 patients initially randomized to the placebo (61.2 percent) were subsequently “crossed over” and given tasquinimod after the initial endpoint had shown a clinical benefit to treatment with tasquinimod.
  • Survival data have now been evaluated at an average (median) follow-up of 37 months.
  • At the time of median follow-up (April 2012), 111/190 evaluable patients (58.4 percent) had died of all causes.
  • Median overall survival times were
    • 33.4 months for men initially randomized to tasquinimod
    • 30.4 months for men initially randomized to a placebo
    • 34.2 months for men with evident bone metastases who were initially randomized to tasquinimod (n = 92)
    • 27.1 months for men with evident bone metastases who were initially randomized to a placebo (n = 44)
  • Based on an adjusted, multivariable analysis, compared to initial treatment with a placebo
    • Progression-free survival data favored tasquinimod (adjusted hazard ratio [aHR] = 0.52).
    • Overall survival data favored tasquinimod (aHR = 0.64).
    • Time to symptomatic progression favored tasquinimod (P = 0.039, HR = 0.42).
  • Toxicities associated with tasquinimod treatment “tended to be mild in nature and improved over time,” but 22 percent of all patients did discontinue therapy because of adverse effects.

The authors also looked at the effects of treatment with tasquinimod on biomarkers such as bone alkaline phosphatase and lactate dehydrogenase (LDH) in the long term and the shorter-term (transient) induction of levels of inflammatory biomarkers, VEGF-A, and thrombospondin-1. They note that, “Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit.”

In their conclusion, Armstrong et al. state that:

The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in [progression-free survival] with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio.

The results of the much larger, ongoing Phase III trial will be needed to confirm this initial conclusion, and the completion date for this larger trial is still a ways off. (The information on estimates this date to be January 2016.) And if the results of the Phase III trial do indeed confirm the data from the Phase II trial, there is then the question of where tasquinimod will “fit” into the evolving paradigm for the treatment of mCRPC. Is it to be used before, after, or in combination with drugs like enzalutamide, abiraterone acetate, and sipuleucel-T? We are not aware (as yet) of any trials designed to address that important question.

One Response

  1. The OS-trend read-out will be during 2014. A not-disclosed number of events will trigger the read-out. Primary end-point is PFS and those data should have been possible to read already during end of summer 2013. If data is positive, tasquinimod might be available as a new possible treatment option during 2015.

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