ADT + enzalutamide in mHSPC … outcome of the ARCHES trial

Pfizer and Astellas have, this morning, announced that the addition of enzalutamide to standard androgen deprivation (ADT) has led to improved outcomes in men with metastatic, hormone-sensitive prostate cancer (mHSPC). This is the first time that a “second-line” form of androgen deprivation has been shown to have meaningful efficacy in the treatment of any form of hormone-sensitive (as opposed to castration-resistant) prostate cancer.

Limited information about the results of this trial are available in a media release from the companies.

The multi-national, randomized, double-blind, placebo-controlled, Phase III ARCHES trial enrolled a total of 1,150 men with mHSPC at sites in the USA, Canada, Europe, South America, and the Asia-Pacific region. Patients were randomized to one or other of two arms of the trial:

  • In the experimental arm, patients were started on or continued on standard ADT (an LHRH agonist or antagonist) or had a history of bilateral orchiectomy and were treated in addition with enzalutamide 160 mg/d.
  • In the control arm, patients were started on or continued on standard ADT or had a history of bilateral orchiectomy and were treated in addition with a placebo.

It should be noted that the trial also included some patients who had received recent treatment with docetaxel-based chemotherapy for mHSPC, but whose disease had not progressed.

The primary endpoint of the trial was radiographic progression-free survival (rPFS), defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review, or death, whichever occurred first.

A summary of the ARCHES trial protocol can be found on the web site.

With regard to the details of the study outcome, all we know at present is that the trial met its primary endpoint. In other words, the combination of standard ADT + enzalutamide must have significantly delayed time to radiographic progression compared to the combination of standard ADT + a placebo. It is possible that we will be able to hear the initial report on the trial outcome in a “late breaking” presentation at the Genitourinary Cancers Symposium in San Francisco in early February next year.

2 Responses

  1. You can also start with enzalutamide monotherapy instead of the combination with ADT used in the ARCHES trial. However, the cost of enzalutamide is much higher than Lupron. See relevant trial results here and here.

  2. Dear George:

    You may be able to obtain enzalutamide monotherapy in Germany, but in most of the world that is not an option because enzalutamide hasn’t been approved as monotherapy for the treatment of any stage of prostate cancer at all, and I don’t know of any insurance system (public or private) that will cover the cost of the product.

    The data you refer to are from a relatively small, Phase II, open-label, pilot study, and the data are not compared to the standard of care, so we have no meaningful information about the relative efficacy or safety of enzalutamide monotherapy as compared to standard forms of androgen deprivation therapy (ADT) as yet.

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