Long-term follow-up data from LATITUDE trial


Long-term follow-up data from the LATITUDE trial have now been published by Fizazi et al. in Lancet Oncology.

The LATITUDE trial initially enrolled 1,209 men, newly diagnosed with high-risk, metastatic, hormone-sensitive prostate cancer (at 235 different suites in 34 countries). Ten of these patients were found to be ineligible, and so 1,199 men were actually randomized to treatment in either

  • Group A: Abiraterone acetate (1,000 mg) once daily + prednisone (5 mg) once daily + standard androgen deprivation therapy (ADT) (n = 597) or
  • Group B: Two matching placebos + standard ADT (n = 602)

Each treatment cycle lasted for 28 days.

Interim results had originally been reported in early 2017 based on data as of October 31, 2016.

After the interim results were initially reported, patients in Group B were allowed to cross over to receive abiraterone acetate + prednisone + ADT in an open-label extension phase of the study (which lasted for 18 months from February 2017).

Here are the core study results as of August 15, 2018:

  • Average (median) follow-up was 51.8 months from time of study enrollment.
  • 618/1,119 patients had died of all causes
    • 275/597 (46 percent) from Group A
    • 343/602 (57 percent) from Group B
  • Average (median) overall survival (OS) was
    • 53.3 months among patients in Group A
    • 36.5 months among patients in Group B
  • OS was significantly longer among the patients in Group A as compared to Group B (hazard ratio [HR] = 0.66; p < 0.0001).
  • The most common Grade 3/4 adverse events were
    • Hypertension in
      • 125/597 (21 percent) of patients in Group A
      • 60/602 (10 percent) of patients in Group B
      • 3/72 (4 percent) of patients crossed over from Group B
    • Hypokalaemia in
      • 70/597 (12 percent) of patients in Group A
      • 60/602 (10 percent) of patients in Group B
      • 2/72 (3 percent) of patients crossed over from Group B
  • Serious adverse events of any grade were observed in
    • 192/597 (32 percent) of patients in Group A
    • 151/602 (25 percent) of patients in Group B
    • 4/72 (6 percent) of patients crossed over from Group B
  • Treatment-related deaths occurred in
    • 3/597 patients in Group A
    • 3/602 patients in Group B
    • 0/72 patients crossed over from Group B

Fizazi et al. conclude that

The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with newly diagnosed high-risk mCSPC and had a manageable safety profile.
They further state that their findings support the use of abiraterone acetate + prednisone as a standard of care in patients newly diagnosed with high-risk, metastatic, hormone-sensitive prostate cancer.
The “New” Prostate Cancer InfoLink would note that what we do not have at this time is any direct, head-to-head comparison between the OS benefit of initial treatment of such patients with docetaxel-based chemotherapy + ADT (as in CHAARTED and STAMPEDE trials) and abiraterone acetate (Zytiga) + prednisone + ADT (as in the LATITUDE trial).
A problem with the use of Zytiga + prednisone is the requirement for long-term use of the corticosteroid prednisone (or prednisolone) for 4 or more years. Side effects of long-term treatment with a drug like predisone are cumulative over time. For some patients the survival benefits may be worth the risk. For others, the risk may outweigh the potential survival benefit.

4 Responses

  1. Is there any benefit associated with abiraterone usage for guys with metastatic, castration-sensitive prostate cancer having been on IADT and having had initial RP, SRT, and subsequent IMRT to pelvic lymph nodes then SBRT to bone metastasis?

  2. Dear Bob:

    I am not aware of any actual data on the use of abiraterone acetate in men who meet the criteria you specify. On the other hand, since it is a systemic form of therapy, there is good reason to believe the drug would have activity in such patients. The unanswerable questions are, “OK. So how much activity and would it extend my life significantly?”

  3. Sitemaster

    Thanks. So far I remain castrate using just estradiol patches after stopping Trelstar. I believe Abi or Enzo add only about 4 months for one in my circumstances. I’m obviously hoping that the patches work for a long time.

    Bob

  4. Dear Bob:

    There are no data that I am aware of that give us insight into the efficacy of “second generation” forms of androgen deprivation (abriraterone, enzalutamide, etc.) in men who have metastatic disease and are either estradiol sensitive or who progress while on estradiol.

    Your estimate of 4 months is presumably based on the results of the original trials of abiaterone acetate and enzalutamide in men who had metastatic, castration-resistant prostate cancer and who had also received docetaxel-based chemotherapy (the worst-case scenario at the time those trials were initiated). That may be a very conservative estimate in your case, but hou are probably right to hope that the estradil patch therapy continues to keep everything under control for an extended period of time.

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