Long-term follow-up data from the CHAARTED trial


At the time of the original presentation of data from the CHAARTED trial, the median follow-up for patients enrolled in this trial was 28.9 months. We now have data from the same 790 patients followed for a median of 53.7 months.

The new paper by Kyriakopoulos et al. has just been published in the Journal of Clinical Oncology. Only the abstract is available on line, and we expect that more detail may be available at the upcoming Genitourinary Oncology Symposium in San Francisco.

Just as a quick reminder, the CHAARTED trial divided patients newly diagnosed with metastatic prostate cancer into two subsets: those with “high-volume”, hormone-sensitive, metastatic prostate cancer and those with “low-volume”, hormone-sensitive, metastatic disease. To have “high-volume” disease a patient had to have

  • Either four or more metastases to bone, with at least one outside of the vertebral column and pelvis
  • Or at least one visceral (soft tissue) metastasis

If patients did not meet the criteria for high-volume metastasis then, by default, they were classified as having low-volume metastatic disease.

All patients were then randomized to treatment with

  • Either androgen deprivation therapy (ADT) + docetaxel (75 mg/m2 for up to six cycles)
  • Or ADT alone

In the initial paper published by Sweeney et al. in the New England Journal of Medicine in 2015, the authors reported that, at a median follow-up of 28.9 months:

  • The median overall survival (OS) for all patients (n = 790) was
    • 57.6 months for those receiving combination chemohormonal therapy
    • 44.0 months for those receiving ADT alone
    • With a hazard ratio (HR) of 0.61
  • The median OS for patients with high-volume disease (n = 513) was
    • 49.2 months for those receiving combination chemohormonal therapy
    • 32.2 months for those receiving ADT alone
    • With an HR of 0.60
  • For patients with low-volume disease (n = 277)
    • Median survival had not been reached

In the new paper by Kyriakopoulos et al., at a median follow-up of 53.7 months, the authors now report that:

  • The median overall survival (OS) for all patients (n = 790) was
    • 57.6 months for those receiving combination chemohormonal therapy
    • 47.2 months for those receiving ADT alone
    • With a hazard ratio (HR) of 0.72
  • The median OS for patients with high-volume disease (n = 513) was
    • 51.2 months for those receiving combination chemohormonal therapy
    • 34.4 months for those receiving ADT alone
    • With an HR of 0.63
  • For patients with low-volume disease (n = 277)
    • No OS benefit was observed
    • The HR was 1.04

Basically, the authors conclude that, at about 5.5 years of follow-up:

The clinical benefit from chemohormonal therapy in prolonging OS was confirmed for patients with high-volume disease; however, for patients with low-volume disease, no OS benefit was discerned.

There are two basic ways to look at these data. One alternative is to take the “glass half full” approach, which is to say that we now know that combination chemohormonal therapy is of great benefit in extending the long-term survival of men diagnosed with high-risk, high-volume prostate cancer (if they have not been treated earlier according to protocols defined in the STAMPEDE and in the LATITUDE trials). The other is to take the “glass half empty” approach one and ask “Why would the low-volume patients not gain a similar benefit?”

Perhaps a more constructive way to look at this is to remember that we do indeed have the data from the STAMPEDE and the LATITUDE trials, which suggest that for men with lower volumes of metastatic disease (and even just micrometastatic disease) the combinations of radiation + ADT + chemotherapy and ADT + abiraterone + prednisone have both been shown to improve long-term survival compared to ADT alone. Thus, we now have three highly effective forms of therapy for first-line treatment of men with low-volume or high-volume, hormone-sensitive, metastatic prostate cancer. The issue is only when to apply which one for the greatest potential benefit in an individual patient.

4 Responses

  1. Sitemaster,

    Can any data from the CHAARTED trial be mined to determine if quality of life was better or worse during the extended survival period when a patient is treated with ADT + docetaxel compared to ADT alone? I just read an article by Dr. Sartor where he examined the data from the LATITUDE trial to conclude that quality of life was actually better in the ADT + abiraterone arm than the ADT + placebo arm (see here).

    Thank you.

    Richard

  2. Dear Richard:

    I would assume that yes, that could be done — again. One study has already been reported on this precise subject, based on the early data from CHAARTED.

  3. Do we have any data on ADT + Xtandi vs ADT + chemo for low volume disease?

  4. Jerry:

    Not that I am aware of (yet).

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