New data from the STAMPEDE trial are again positive


This afternoon, James et al. will report the full details from the most recently completed component of the STAMPEDE trial (see NCT00268476). However, data from the abstract are already available.

In this component of the STAMPEDE trial, James and his colleagues randomized men with high-risk, locally advanced prostate cancer or metastatic prostate cancer to either

  • Standard of care (SOC) , with androgen deprivation therapy (ADT) for 2 or more years and appropriate radiation therapy (which was mandated for men with N0M0 disease and encouraged for men with N+M0 disease) or
  • SOC + abiraterone acetate (1000 mg/day) + prednisolone (5 mg/day)

Between November 2011 and January 2014, the research team randomized 1,917 patients to one or other of these arms of the trial. Here are the core results:

  • The patients were well balanced between the two arms of the trial.
    • Average (median) patient age was 67 years.
    • 52 percent of the patients had metastatic (M1) disease.
    • 20 percent of the patients had N+M0 or NxM0 disease.
    • 28 percent of the patients had N0M0 disease.
    • 95 percent of the patients were newly diagnosed.
    • Average (median) patient PSA level was 53 ng/ml.
    • Average (median) follow-up was 40 months.
  • 262 patients died in the SOC alone arm of the trial (and 82 percent of these men died of prostate cancer).
  • 184 patients died in the SOC + abiraterone + predisolone arm of the trial.
  • The adjusted hazard ratio (aHR) for overall survival for the SOC + abiraterone + predisolone arm of the trial compared to the SOC alone arm was 0.63 (p = 0.115 × 10-7).
  • The overall survival rate at 3 years improved from 76 percent for the SOC alone arm to 83 percent for the  SOC + abiraterone acetate + prednisilone arm.
  • In terms of other outcomes, there were
    • 535 failure-free survival events in the SOC + abiraterone + prednisolone arm
    • 248 failure-free survival events in the SOC alone arm
    • This difference was also highly statistically significant (aHR = 0.29; p = 0.377 × 10-63)
  • Grade 3 adverse events were seen in
    • 29 percent of patients on SOC
    • 41 percent of patients on SOC + abiraterone + prednisolone
  • Grade 4 adverse events were seen in
    • 3 percent of patients on SOC
    • 5 percent of patients on SOC + abiraterone + prednisolone
  • Grade 5 adverse events (i.e., adverse events causing patient deaths) were seen in
    • 3 patients on SOC alone (of which 1 was treatment-related)
    • 9 patients on SOC + abiraterone + prednisolone (of which 2 were treatment-related).

James and his colleagues conclude that the results of this large trial

show a clinically and statistically significant effect on overall survival and failure-free survival from adding abiraterone at start of ADT with a manageable increase in toxicity. ADT [± radiation therapy as appropriate] + abiraterone is a new standard of care for this group.

The “New” Prostate Cancer InfoLink would note that the potential risk for increased side effects is not negligible, and so clinicians will need to apply this new standard form of care with some caution.

The unanswered question is whether we now need to compare ADT + abiraterone + predisolone to ADT + docetaxel chemotherapy + prednisone or prednisolone in this group of patients. James and his colleagues seem to be suggesting that the improvement in outcomes offered by ADT + abiraterone + prednisolone renders that trial unnecessary.

3 Responses

  1. Is it possible to calculate how long on average the SOC survived vs. SOC + Abi? Meaning, how many more months did they survive. Sorry if that info is posted and I’m just missing it.

    Also, I’m assuming the placebo arm was able to go on to other therapies after failed HT, including Abi?

    Thanks,

    Jerry

  2. Dear Jerry:

    Please click here to see the full data from the STAMPEDE trial as reported in the New England Journal of Medicine. So, with regard to your questions …

    (1) We can’t answer your first question because in none of the data sets had the patients who were treated with SOC + abiraterone reached 50% survival at the time the study was stopped. However, if you look at the data on overall survival (see pp. 4, 6, and Figure 1 in the paper mentioned above), they will give you a very clear idea of the difference in survival rates over time.

    (2) All patients who had progressive disease on either SOC alone or on SOC + abiraterone were eligible for treatment with other forms of therapy at their physicians’ choice. If you look at p. 9 and Figure 3 of the above-mentioned paper, it will tell you exactly how patients were managed after progression, but the effects of the different treatments after progression are not clear yet because of the relatively short periods of time for which only relatively small numbers of patients have been treated after such progression.

  3. We always speak of a median survival difference, that is, how many extra months did 50% of the men survive because they were randomized to one therapy vs. the other. As the Sitemaster said, the median was not yet reached in the abiraterone arms in the limited follow-up of these two trials. For my own edification, I decided to look at the 60% survival, which did seem to have been reached in both cases. I noticed the survival curves were very separate and diverging at that point, so that the 60% survival difference is very likely smaller than the 50% survival difference will turn out to be on future follow-up. Based on my, admittedly clumsy, pencil and straightedge calculation, the 60% survival difference was 18 months in STAMPEDE and 12 months in LATITUDE, so we can reasonably expect the median survival differences to be larger than those amounts.

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