Final CHAARTED data now published in NEJM

The final results of the CHAARTED trial, recommending early treatment with the combination of androgen deprivation therapy (ADT) and chemotherapy, at least in men with extensive metastasis at diagnosis, have just been published this week by Sweeney et al. in The New England Journal of Medicine (NEJM).

The final published results appear to be closely analogous to those originally reported at ASCO in 2014.

The full text of this paper has been made freely available to all readers by the management of the NEJM — so you are encouraged to read either the entire paper or at least the abstract for yourself. The combination of these data with the data reported from the STAMPEDE trial at ASCO in 2015 has now provided compelling evidence supporting combination therapy (with ADT and docetaxel-based chemotherapy) for men newly diagnosed with metastatic prostate cancer — and most particularly for those men initially diagnosed with more extensive forms of metastatic disease.

8 Responses

  1. How is “metastatic” defined for purposes of this trial? I have stage pT3b gleason 9 PCa, and PSA has been on the rise again after coming off six months of lupron during and after SRT (IMRT) following failed RP. PET Scan Choline c-11 showed no mets and I am asymptomatic. So any cancer I have is micro metastatic, which I don’t believe is defined as “having mets”. I’m in the process of selecting a medical oncologist to discuss what’s next.

  2. Dear Bob:

    In the CHAARTED and the STAMPEDE trials, “metastatic” meant evident metastasis on a bone scan, so you are correct, you would not meet the definition for metastasis used in these two trials. However, that does not necessarily mean that early chemotherapy would be a bad idea given your situation. You will need to discuss this possibility with an appropriately knowledgeable medical oncologist.

    If you wanted to join our social network, we could talk to you in more detail about all your possible options. One of the key questions is what your current PSA doubling time might be.

  3. Is there another trial which concludes that, upon diagnosis with metastatic disease, ADT alone, then chemotherapy when castration resistance occurs, results in shorter overall survival than combined ADT + chemotherapy as the initial treatment? I am not surprised that adding an additional therapy to ADT results in longer survival, but wouldn’t the applicable question be whether adding chemotherapy early or later is better for survival, given that chemotherapy comes with its own additional side effects (from a QOL perspective)? Thank you.

  4. Dear Richard:

    In both the CHAARTED and the STAMPEDE trials, men in the initial ADT-alone arm and the initial ADT + chemotherapy received other treatments once their disease progressed, but the precise form and order of those treatments depended upon exactly when the men in the trials progressed and what else was available to them at that time. As an example, the men enrolled earliest in the two trials who were initially treated with ADT alone were most likely to get docetaxel-based chemotherapy as their second-line treatment because neither abiraterone acetate (Zytiga) nor enzalutamide (Xtandi) would have been available to them outside of another clinical trial. And until 2013 nether of these drugs had show effectiveness in metastatic, castration-resistant prostate cancer prior to treatment with chemotherapy.

    Thus, while docetaxel-based chemotherapy was not specified as second-line therapy for the men in the initial ADT-only arms of these two trials, it would almost certainly have been the second-line therapy of choice for the vast majority of them.

    If you look at the full text of the CHAARTED trial (see link above), you will see that the quality of life issue related to the side effects of chemotherapy is dealt with in detail. Similar effects were apparent in the STAMPEDE trial, but we haven’t seen the full, published data for this trial yet. The bottom line appears to be that, on average, for men with a significant tumor load when initially diagnosed with metastatic disease, the survival benefit associated with combination treatment appears to far outweigh the risks associated with the side effects of adding the chemotherapy. However, only the individual patient can make individual decisions about his personal views of that risk.

    It would be unethical, today, to do a trial in which one compared ADT + chemotherapy up front to ADT followed by chemotherapy at the time of treatment failure because both abiraterone and enalutamide have now been shown to extend survival more than chemotherapy alone when given prior to chemotherapy in men who become resistant to standard first-line ADT.

  5. Have there been any studies which showed the survival rate of men with Gleason 9 PCa who chose not to have any further treatment after failed RP and SRT?

  6. Bob:

    I am not aware that anyone has ever done such a study (at least in the past 30+ years), but there is a 99.99% certainty that such men will, over time, progress to having metastatic disease, and that disease will kill them, painfully, if they have no further treatment. The question is going to be when you choose to to start treatment as opposed to “whether”. The slower your PSA is rising, the longer you can put treatment off.

  7. The jury seemed to be out for the low volume guys last year. Has anything changed in this regard? Thanks.

  8. No Jerry. The jury is still “out” for men with relatively low amounts of metastatic disease (say just one or two small mets in the spine). IR will probably take at least a couple more years before data on these men specifically is available from either the CHAARTED or the STAMPEDE trials.

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