Update on STAMPEDE data on abiraterone + ADT in M0 patients with HSPC


Three months ago, James et al. presented the overall survival data from the most recently completed arm of the STAMPEDE trial at the annual meeting of the American Society of Clinical Oncology (ASCO).

At that time, they were able to tell us that there was an absolute overall survival benefit of 7 percent from treatment of the hormone-sensitive prostate cancer (HSPC) patients with androgen deprivation therapy (ADT) + abiraterone acetate (Zytiga) + prednisolone as compared to the standard of care (SOC) with ADT at just 3 years of follow-up, with an adjusted hazard ratio of 0.63 (p = 0.115 × 10-7). These data encompassed all 1,917 men enrolled in this arm of the study. In and of itself, that is a set of very significant data.

At the annual meeting of the European Society of Medical Oncology (ESMO) in Madrid, which has now closed, James et al. provided an update to their data from this trial, focused on the outcomes of the patients diagnosed and enrolled with N0M0 disease as compared to the patients with N+M0 disease. (And once again we are indebted to Dr. Zachary Klaassen of the University of Toronto, Princess Margaret Cancer Centre, and to UroToday for their report on this presentation by Dr. James.)

In this arm of the STAMPEDE trial the, standard of care was ADT for 2+ years, and radiotherapy was

  • Mandated for patients with N0M0 disease (unless contraindicated)
  • Encouraged for patients with N+M0.

Stratified randomization allocated patients 1:1 to SOC with ADT or to SOC + abiraterone acetate + prednisolone.

Patients were continued on abiraterone treatment until there was evidence of PSA, radiological, and clinical progression, capped at 2 years in patients receiving radiotherapy. The definitive primary outcome measure was death from any cause and failure-free survival (FFS) was the intermediate primary outcome measure. Secondary outcomes included metastasis-free survival (MFS).

In Madrid, James et al. reported that

  • 915 patients with NoM0 or N+M0 disease were randomized to SOC or SOC + abiraterone + prednisolone from November 2011 to January 2014.
  • Among these 915 patients
    • Average (median) age was 67 years.
    • 81 percent were WHO performance status 1.
    • 42 percent had N+M0 disease.
    • Average (median) follow-up was 38 months.
  • N0M0 patients who were not planned for radiotherapy (because they had been previously treated or because radiotherapy was contraindicated) were not excluded from subgroup estimates.
  • Overall rates of FFS at 3 years were
    • Improved among N0M0 patients treated with SOC + abiraterone + prednisolone compared to SOC (hazard ratio [HR] = 0.14)
      • 80 percent among N0M0 patients treated with SOC
      • 98 percent among N0M0 patients treated with SOC + abiraterone + prednisolone
    • Improved among N+M0 patients treated with SOC + abiraterone + prednisolone compared to SOC (HR = 0.26)
  • Estimated rates of MFS at 3 years were
    • Favorable for SOC + abiraterone + prednisolone in both subgroups, i.e.,
      • HR = 0.62 for patients with N0M0 disease.
      • HR = 0.47 for patients with N+M0 disease.
  • Estimation of rates of overall survival in patients with N0M0 disease is not yet possible, with only 26 deaths among the N0M0 as of the time of the current analysis.

James et al. apparently concluded that early clinical outcomes for all M0 patients who were treated with SOC + abiraterone acetate + prednisolone were excellent, particularly for the N0M0 patients also planned for radiotherapy.

They also pointed out (as we have also reported elsewhere) that improvements of this magnitude in MFS among M0 patients should translate into a survival advantage.

7 Responses

  1. How does this apply to me with HSPC, node mets radiated and no recurrence, PSA stable at 0.3. In other words, if node and bone mets are no longer are evident due to RT and SOC ADT, is Zytiga + prednisone indicated?

    Bob

  2. Dear Bob:

    Well in my opinion, if you are currently PSA stable after radiation + ADT, then no, you don’t need to have further treatment at this time, but this is a question you really need to ask your doctor. The full implications of the results of this arm of the STAMPEDE trial have still to be resolved.

  3. These data are interesting because 42% of the M0 patients were found to be N+M0. Whereas radiotherapy was mandated for N0M0 patients, it was optional for patients with N+M0. So indirectly the study opens for the analyses — what happens for N+M0 patients if they get radiotherapy or not. Does it help or does it prove to be ineffective? Further, will radiotherapy be potentiated from abiraterone + ADT more than with ADT alone?

    So with clear answers for these questions, the study may have far-reaching consequences for renewal of guidelines for management of N+M0 patients.

  4. Dear Sitemaster,

    Since it is currently quite common for patients to be treated with first-line ADT agents alone until the point of CRPC, and then add agents like abiraterone/prednisone, wouldn’t it have been more appropriate to have this sequential protocol as a third arm which could then be compared to the upfront use of abiraterone + prednisone or prednisolone + ADT?

  5. I’m not sure what is being compared here. Were the men on RT + ADT capped at 2 years of ADT also? If not, the 3-year FFS includes 2 years of ADT + abiraterone after RT, but may be < 2 years of ADT after RT for the control group? This is very muddy. Why can't they just look at the high risk (M0) men who had RT + 2 years of ADT and compare it to those who got RT + 2 years of ADT + Zytiga?

  6. Dear Len:

    In an ideal world, yes, but I doubt if the manufacturers of abiraterone would have been willing, at the time this trial was started, to provide free drug for that third arm of the trial.

  7. Dear Allen:

    I think we’ll have to wait to see the full publication of these data to see if they offer any clarity regarding that question.

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