Abiraterone (Zytiga™) earlier makes a big difference in outcomes

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The big news at the ASCO annual meeting this year included two “practice changing” presentations for prostate cancer that have been widely covered in the medical press. The basic finding is that adding abiraterone to ADT in the “up front” setting (i.e. when initially starting ADT for high risk disease, a rising psa or in someone who has newly diagnosed metastatic disease) results in markedly improved overall survival and time to progression of disease. I encourage you to read the link above which reviews the presentations and commentaries in detail. Reflecting our amazing digital age, the New England Journal published the detailed, peer-reviewed articles on the two studies simultaneously with the ASCO presentations.

In the Latitude trial, 1199 men who were newly diagnosed with metastatic disease and who “… were considered to have at least two high-risk prognostic features (e.g., a Gleason score of ≥8, the presence of ≥3 bone lesions, or the presence of measurable visceral metastasis)” were randomized to receive a GnRH analog plus abi/prednisone vs GnRH analog plus dual placebos. The science behind this is that with surgical (orchiectomy) or medical (GnRH analog) castration, testosterone synthesized by the testicles is mostly eliminated. But there is still stimulation of the prostate cancer androgen receptors (AR) by other testosterone, coming from the adrenal glands, the tumor cells making testosterone themselves,  other steroids, or even changes in the androgen receptor itself. Abiraterone or its metabolites can block most of these pathways. Thus the question is whether nearly complete shutdown of AR stimulation from the onset of treatment can achieve more than waiting to use Abi after resistance to AR directed treatment with a GnRH analog develops. The results were remarkable:

A second trial, from the STAMPEDE group used a similar approach in a different, more heterogeneous group of 1917 patients with high risk localized disease, metastatic disease, or PSA relapsing disease after local therapy. The randomization to standard ADT alone vs ADT plus Abi/prednisone was similar as were the remarkably positive outcomes.

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The P-values for some of the endpoints in this trial were eye-popping. “Time to failure improved by 71% in the abiraterone group (HR 0.29, 95% CI [0.25, 0.34]; p = 0.377×10-61)” The discussants at ASCO pointed out that future trials may need to consider comparison of abiraterone early addition to the early addition of chemotherapy as was done in the CHAARTED trial. Generally, however, the toxicities of docetaxel are certainly greater than abiraterone and such a trial would be complicated. It is even possible that one of the ways docetaxel works is “simply” blockade of AR translocation and that it is just a more toxic way of hitting the same pathway. In addition, the cost considerations of abiraterone, particularly when it must be taken for years, are a real concern, and in keeping with the very keen worries we have regarding new cancer drugs in general.

“Targeted therapies” along with the immune checkpoint blockade drugs are changing the landscape for cancer patients. To me, the somewhat surprising thing about these two studies is how great the advantage seems to be when you can truly effectively hit a target early and hard, in this case the AR signaling pathway. It is all the more remarkable that this is a pathway we have now been targeting for over 70 years and there is still more to come. If we can find the right combination of AR targeting and immune modulation, I see no reason why metastatic prostate cancer can’t be added to the “curable neoplasm” list in the near future. Then the question of whether, and how we need to screen will become even more complex. Good news !!

Disclaimer: I am a consultant for Janssen, the pharmaceutical company that sponsored the Latitude trial discussed above.

 

5 Comments

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5 responses to “Abiraterone (Zytiga™) earlier makes a big difference in outcomes

  1. john c miller

    CAN we talk about the COST. $9200 for a months dosage! The profit making pharmaceutical companies! John currently taking it!

  2. Maegan Jones

    Hi Michael,

    Healthline would like to congratulate you on making our list of the Best Prostate Cancer Blogs of 2017!

    Our editors carefully selected the most up-to-date, informative, and inspiring blogs that aim to uplift their readers through education and personal stories. We’re glad to have you on the list!

    We’ve created a badge that you can embed on your site to let your readers know about your win. The embed code is at the link below.

    Winners list: http://www.healthline.com/health/prostate-cancer/best-blogs-of-the-year
    Badge to embed: http://www.healthline.com/health/prostate-cancer/best-blogs-badge-2015

    If you have any questions or need help embedding the badge, feel free to be in touch. Congratulations and keep up the great blogging!

    Warmly,
    Maegan


    Maegan Jones | Content Coordinator
    Healthline
    Your most trusted ally in pursuit of health and well-being

    • Thanks. However, your list seems to refer to me as a patient who had advanced metastatic disease etc. That is not me, but a urologist I blogged about. I am a treating physician and you can read about me on the “about” link.

  3. Terry Maalen

    Of course you are a consultant for Janssen. Reading it only made me sadder. Disgraceful how my husband who desperately needs this as his last chance after going thru every possible treatment for 11 years, can’t get it because of the cost. I think Janssen is heartless and cruel.

  4. Pingback: Rising PSA – When to start therapy | prost8blog

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