Intermittent vs. continuous ADT: a therapeutic meta-analysis

According to the results from a new meta-analysis of data from 15 different clinical trials in nearly 7,000 patients in total, intermittent androgen deprivation therapy (ADT) is not inferior to continuous ADT with respect to the overall survival of patients. However, the authors clearly have some reservations about this conclusion.

Magnan et al. have just reported their results in the journal JAMA Oncology. They had set out to conduct

a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer.

To do this, they searched for studies in a wide variety of relevant databases through to March 2014, focusing on identifying papers with overall survival and quality of life as the primary endpoints and cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects as secondary endpoints.

Here are the core study findings:

  • They based their analysis on data from 6,856 patients reported in 22 published articles from 15 trials — all published between 2000 and early 2014.
  • 14/15 studies (93 percent) had either an unclear or a high risk of bias in the data presentation.
  • There were no significant differences between men receiving intermittent ADT and continuous ADT with respect to
    • Overall survival (hazard ratio [HR] =1.02), based on data from 8 trials and 5,352 patients
    • Cancer-specific survival (HR = 1.02), based on data from  5 trials and 3,613 patients
    • Progression-free survival (HR = 0.94) based on data from 4 trials and 1,774 patients.
  • There was “minimal difference” in quality of life between the two forms of treatment (based on self-reported data from patients).
  • In most trials of the 15 trials there was some degree of improvement in physical and sexual functioning with intermittent as opposed to continuous ADT.

In their conclusions the authors state clearly that, “Intermittent [ADT] can be considered as an alternative option [to continuous ADT] in patients with recurrent or metastatic prostate cancer.” However, their statement about “unclear or high risk of bias” among 14 of the 15 studies they identified as being relevant to this analysis is clearly an issue that concerned them.

One of the problems with even the largest studies of intermittent as compared to continuous ADT conducted to date has been that they have (arguably) failed to appropriately stratify differing categories of patients into sufficiently well-defined groups and also failed to ensure that patients met some really sound criteria to suggest that they could only be randomized to intermittent or continuous ADT depending on sufficiently good responses to the first 6 or 9 months of ADT given to all patients. As a consequence, we still lack really clear information about which patients are really “the right” types of candidate for intermittent ADT.

We know, in principle, that some men really do benefit greatly from intermittent as opposed to continuous ADT. We also know that some men absolutely do not gain such benefit. What we do not really know at this time is how best to identify those different subsets of patient and differentiate between them and a group of patients “in the middle ground” for whom the value of one form of treatment over the other is probably very limited.

2 Responses

  1. As a bone met, Gleason 9 guy, I never thought I could do IHT, but have been on a hormone therapy vacation for 3 years. I know I’m going to have to go back on some therapy soon, but it’s been nice not dealing with the side effects for such a long period of time.

    When I’m on certain therapies it’s nice to know that there might be a chance down the road that I can have another vacation.

    If CHT had overwhelmingly better survival benefits I’d have to reevaluate.

    If I could truly have my way, I would go with NHT — No Hormone Therapy.

  2. I’m happy to see some research (shortcomings understood) affirming that there are at least no significant negative outcomes for IHT. I am coming off 18 months of Lupron therapy (2009 RALP, 2013 radiation) and after almost 2 months of “vacation” I have welcomed the absence of “brain fog”, sweats, severe headaches, and fatigue. I don’t know if my earlier weight gain and loss of muscle tone is remediable but I’m making efforts to find out. Nor, of course, can I tell how long I will stay off the injections. After my first quarterly PSA test, my oncologist and I will discuss what a possible trigger point would be for going back on the Lupron. This has been — so far — a positive result in terms of QOL, and at age 73 I do welcome that!

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