Data from the LATITUDE trial to be presented at ASCO

According to an e-mail your sitemaster has just received from ASCO, we will be getting the initial results from the LATITUDE trial at the upcoming ASCO meeting in June this year.

The LATITUDE trial is a randomized, double-blind, placebo-controlled, Phase III trial in which newly diagnosed men with high-risk, metastatic, hormone-naive prostate cancer (mHNPC) were randomized to treatment with either

  • Abiraterone acetate (Zytiga) + low-dose prednisone + androgen deprivation therapy (ADT) or
  • ADT alone (i.e., ADT + two different placebos instead of the abiraterone and the prednisone)

The trial was designed to enroll some 1,200 patients at over 200 study centers around the world. It was initiated back in 2012, several years before we had data from the CHAARTED and the STAMPEDE trials both showed survival benefits in men newly diagnosed with metastatic prostate cancer.

So, one of the problems with the LATITUDE study is that out in “the real world” few mHNPC patients would normally receive ADT alone as first-line therapy today because of the results of the CHAARTED and the STAMPEDE trials.

We will need to wait to hear the actual results of the LATITUDE trial, but they will probably have to show a major long-term survival benefit if this type of therapy is to have a chance of replacing initial treatment of mHNPC patients with the current standard of ADT + docetaxel-based chemotherapy (with the addition of radiation therapy in appropriate patients).

5 Responses

  1. The STAMPEDE trial group will also be presenting our abiraterone results. We have data on just under 2000 patients, with mature follow-up for overall survival. Inclusion criteria include not just M1 (as in LATITUDE) but also high-risk M0.

  2. Form of ADT in the LATITUDE trial

    The form of ADT is either an LHRH agonist drug or surgical castration.

    This contrasts to combined therapy with an LHRH agonist (or now Firmagon — an LHRH antagonist), or castration, plus an antiandrogen (usually bicalutamide/Casodex at a dose of 150 mg for metastatic patients, and perhaps a 5-alpha-reductase inhibitor drug (preferably dutasteride/Avodart if genetically suitable).

    The form of ADT in the LATITUDE trial is the most basic form in use.

  3. And the form of ADT described by Jim Waldenfels has never been shown to offer a survival benefit compared to the “most basic” form of ADT — in either men newly diagnosed with metastatic prostate cancer or in men progressing to having metastatic prostate cancer.

  4. My understanding is that it triple ADT has not been tested against ADT monotherapy, such as by surgical castration or an LHRH-agonist. However, the results of a trial of combined blockade – an LHRH-agonist plus flutamide – were reported about two decades ago:

    PMID: 9519355 Eur Urol. 1998;33(2):144-51. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. From the results section: “…Additionally, maximal androgen blockade [meaning combined blockade as described above versus surgical castration] treatment showed significantly better results for duration of survival (p = 0.04), time to death due to malignant disease (p = 0.008), time to first progression (p = 0.009) and progression-free survival (p = 0.02)….”

    The participants all had metastatic disease, which is not a good setting for ADT.

    There have been other trials and clinical series, some being randomized, but this 1998 paper is probably the earliest report.

  5. Dear Jim:

    (1) The trial you refer to was nothing like the first. The first one was done by Crawford et al. and was published in the NEJM in 1989. It showed a 7-months survival benefit for Lupron + flutamide vs. Lupron + a placebo — and no one has ever been able to replicate that result!

    (2) The trial you refer to was barely statistically significant and has long been considered to be flawed in a number of ways.

    You can beat a dead horse as much as you like, but that won’t bring the horse to life.

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