Other significant news from the ASCO annual meeting

We apologize for the slight delay in getting to other notable news from the annual meeting of the American Society for Clinical Oncology. (Other elements of the rest of life interfered.) However, here is the keypoint summary with links to the relevant abstracts:

  • A follow-up analysis of the results of the randomized, Phase III, ALSYMPCA trial of radium-223 in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC), reported at the meeting by Parker et al., has shown that the median overall survival of men in the radium-223 arm of the trial was actually 3.6 months longer than that of men in the placebo arm of the trial (with a hazard ratio [HR] of 0.695). This should be contasted with the overall survival benefit of just 2.8 months initially reported at the time of the original data analysis almost exactly a year ago. Patients enrolled into this trial had all either progressed after treatment with docetaxel-based cheomotherapy, were unfit for treatment with docetaxel, or had declined this treatment option. It is also worth noting that the median time to a first skeletal-related event (SRE) was also prolonged among men treated in the radium-223 arm of this trial compared to the placebo arm (15.6 vs 9.8 months; HR = 0.658).
  • Similarly, a follow-up analysis of data from the randomized, Phase II, clinical trial of tasquinimod vs. placebo in the treatment of men with mCRPC has now shown the possibility of  an overall survival benefit from treatment with tasquinimod (see abstract of paper presented by Armstrong et al.). In this study, men on the tasquinimod arm of the trial had an overall survival of  34.2 months as compared to 30.2 months for the men treated with placebo. Similarly, the median time to death in the subgroup of men who met  the Prostate Cancer Working Group 2 definition for bone metastasis and who were treated with tasquinimod was 34.2 months as compared to 25.6 months for a similar subset of men treated with placebo. This trial was to small to demonstrate statistical significance, and of course a Phase III study of tasquinimod is now being conducted to see if  such an overall survival benefit can actually be proven in a large, prospective, randomized clinical trial.
  • Klein et al. reported additional data on a new, biopsy-based, genomic test designed to improve discrimination of clinically aggressive from indolent prostate cancer. Dr. Klein appears very confident that this test will be extremely helpful in differentiating between aggressive and indolent disease. However, it has to be understood that this test will still require patients to undergo PSA testing and a biopsy in order to identify risk for prostate cancer and confirm a diagnosis. Given these problems, if the test can clearly distinguish between indolent and aggressive forms of prostate cancer with > 75 percent accuracy, it would certainly help to advise those men who could be well managed on active surveillance as opposed to those who need early, aggressive treatment.
  • Morris et al. reported data from a Phase I clinical trial of a completely different type of therapeutic agent (known as ASG-5ME) in the treatment of men with mCRPC and a median PSA level of > 200 ng/ml. This is a very early stage trial, and it would be premature to try to make any decisions about the real clinical potential of this agent, but it is interesting to see that such a very different therapeutic approach does appear to have clinical activity in mCRPC and that it will therefore, presumably, be moved forward into Phase II clinical trials. ASG-5ME is a combination of a fully human antibody to a protein known as SLC44A4 (found in about 95 percent of men with prostate cancer) and a microtubule-disrupting agent called monomethyl auristatin E; such evolving combination therapies are usually referred to as antibody-drug conjugates or ADCs.
  • The continuing debate over the appropriate use of PSA testing was a background to many of the sessions on prostate cancer at the meeting. However, it is interesting to note that, in a newly published book on prostate cancer for patients, Dr. H. Ballentine Carter from Johns Hopkins appears to claim a very similar postion on this issue to that taken by The “New” Prostate Cancer InfoLink. According to information being made availoable to the media, Dr, Carter states, “… not every man needs annual testing, that a baseline PSA can determine the optimal frequency of PSA testing, and that older men with low PSA levels during life can safely discontinue testing.” Dr. Carter is a highly regarded specicialist in the diagnosis and management of early stage prostate cancer and one of the men behind the development of the Johns Hopkins active surveillance protocol that has now enrolled > 1,000 patients. Those who are interested can find his new book (The Whole Life Prostate Book) on line on the Amazon.com web site and elsewhere.

5 Responses

  1. The Klein report sounds just like the kind of strong indicator of aggression for prostate cancer needed.

    Even those who choose surgery at all costs should want their surgeons armed with this and every probability indicator. There is that art factor of nerve-sparing surgery regarding which I, for one, would want my surgeon to be as forewarned about aggression as possible before they start.

    How available is the test? Forecasts of availability?

  2. I was hoping for a larger improvement in OS on the updated analysis from ALSYMPCA. It has moved from 2.8 months median OS benefit on previous analysis to 3.6 months with the latest data.

    I recognise that this patient population is post-docetaxel mCRPC, and that the 3.6 months is a median, but nonetheless …

    Don’t get me wrong … we’ll take the 3.6 months, but what I struggle to understand is why this intervention doesn’t have a larger impact. I am given to understand that the bone metastases are the major cause of mortality in prostate cancer. How do the metastases actually contribute to mortality please? And if Alpharadin is having a significant impact on the metastases, why isn’t the OS benefit longer from an agent that impacts them?

    I don’t wish to sound ungrateful but would just like to improve my understanding on this area.

    Thanks in advance for any insights.


  3. Mike:

    I would think there might be another year’s work needed on this test before anyone was ready to submit data to the FDA for an approval.

  4. Jonathon:

    The cause of death of the majority of men with metastatic CRPC is actually organ failure. The metastases are what initiates such organ failure, but you ned to appreciate that by the time those metastases are visible in any specific organ (from the bones in the spine to the tissues of the liver and the brain), the metastases may have been growing for quite a while.

    The ability to actually “cure” anyone who has mCRPC may actually be limited by comparison with the potential ability to “cure” men who have very early metatstatic or micrometastatic disease. It is going to take a while to work some of this out in detail by initiation of trials with some of these new drugs.

  5. Sitemaster,

    Thank you. It is an odd battle between fast track and safety. With hundreds of biopsies performed every day anyway, and no further risk to anybody, it would be a great way to begin that data base for the future. Banking lab samples now (if that is even possible) would provide the match for later results.

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