The American Society of Clinical Oncology (ASCO) has just released the abstracts of papers to be presented at the upcoming annual meeting in Chicago, starting on Friday, May 31.
For those interested in looking through these abstracts themselves, there appear to be about 475 that deal with prostate cancer. You can review these abstracts if you click here. They will probably not include any of the late-breaking abstracts because those are not usually released until the day of presentation.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: 2019, abstract, ASCO |
THE "NEW" PROSTATE CANCER INFOLINK 
Provenge Markedly More Effective Among African American Men!
Whew! That’s a lot of posters involving prostate cancer! Thanks for posting this list.
The fifth on the list caught my eye at a quick glance. This is Abstract #5035, Poster #147, and the authors include many of the heavy hitter researchers we know.
This poster has results for the PROCEED trial (NCT01306890 – for mCRPC patients) that involve comparison of overall survival in African American and Caucasian men with large numbers of patients involved from a world-wide registry. There is markedly superior response in African American men, with an especially striking difference for men with PSAs below the median: 29.48 ng/ml: median OS for the African Americans was 54.3 months vs. 33.4 months for the Caucasians.
Dear Jim:
It has been clear for a while (as mentioned in this abstract) that African American men did better than the Caucasian men when treated with sipuleucel-T in this study. However, I should point out that this sort of subanalysis of data from large registry studies that was not prespecified in the study design does need to be treated with a great deal of caution, and in truth has to be seen as “hypothesis generating” as opposed to clinical proof of a racially based benefit favoring African American males.
Provenge — The Significance for Patients — Especially AA men — of the Foregoing Abstract (#5305)
Dear Sitemaster:
Thanks for your reply. Your perspective is important and your points are well-taken, of course.
However, as a now savvy patient with an extensive educational background in statistics and experimental design, I switch from one pair of glasses to another when viewing this kind of news. The science glasses show that the hypothesis re benefit to AA men needs following-up with research in a trial. Amen to that! On the other hand, the patient-with-a-once-life-threatening-case glasses reveal that it will likely be years before we get those results, and, if I were an African American man with metastatic CRPC, faced with a decision whether to take a course of Provenge therapy, this research would encourage me to do so, despite the uncertainty that you rightly spotlight.
Dr. Gerald Andriole, MD, included the earlier news that you mention in his presentation at the PCRI-sponsored 2018 Prostate Cancer Conference in September at Los Angeles. He showed a slide from Dr. Sartor and team’s AUA 2017 conference that showed notably better median overall survival of 37.3 months vs. 28 months for AA men compared to Caucasian men; he emphasized that that result was fully unexpected. (Disc 1: 1:06:00)
Speaking at the same conference about treatment for advanced disease but not focusing on Provenge for AA men, Dr. Evan Yu, MD, noted the short time window for use of Provenge that was set by the requirement that patients had to have no symptoms as well as being mCRPC (Disc 1: 2:01:20). He also reviewed research showing that there was an enhanced survival benefit if patients had a lower PSA at baseline, with 41.3 months median survival in patients if their baseline PSA was less than 22.1, compared with some, though considerably less, average benefit even with higher PSAs (such as 27.1 months if the baseline PSA was in the range from 22.1 through 50.1). He said he usually wants a patient with lower and slower moving PSAs when instituting Provenge therapy. (Disc 1: 2:03:50)
Wearing my patient’s glasses, all of this is relevant if we are patients with mCRPC in that short window of time to decide whether we want to have Provenge therapy. Hopefully future research will make these decisions much easier, but this is what we have to deal with now.
Dear Jim:
I fully appreciate the “patient-with-a-once-life-threatening-case glasses” perspective. However, taking Provenge is not benign, and I suggest you try looking at these data with a set of well-polished statistics glasses. I would point out that the numbers of AA men in this study are very small, which makes the risk for misinterpretation very high.
Having said that, I would certainly not blame any AA male with early mCPRC and a relatively low PSA level from thinking that trying Provenge was a good idea. It is indicated for such patients (regardless of race). Nor would I discourage him from seeking such therapy. However, what I would also tell him, if my opinion was requested, is that I feel it might be unwise to conclude from these data that he would necessarily do any better than the white guy with exactly the same clinical profile undergoing leukaphoresis prior to his Provenge therapy in the next cubicle!
Update of the “Halabi Nomogram” for predicting overall survival in mCRPC patients treated with docetaxel (#7 in Siteamaster’s list)
(“External validation of a prognostic model for overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC Abstract #5022, Poster 134))
As a newly diagnosed patient, one of the first questions is, “How long I am likely to survive?” We now know that survival is outstanding for most prostate cancer patients, nearly the same as for our age mates who do not have the disease. But survival still tends to be much shorter for those diagnosed with metastatic disease, and it is also shorter for men who develop metastatic disease. This research provides detailed survival estimates for men with metastases after they no longer respond to hormonal therapy (mCRPC) and who have had treatment with docetaxel.
In simplified terms, a key piece of the abstract is that for the low-, intermediate- and high-risk groups, median overall survival was 29.7 months, 19.0 months, and 12.1 months respectively. These figures do not include the impact of some of the drugs that have become available in recent years, as I understand it. In effect, these figures can serve, in my layman’s view, as rough benchmarks for interpreting the effectiveness of some modern treatments. Sitemaster?
As I understand it, this research updates the earlier nomogram update published in 2014.
As in the 2014 update, the nomogram being updated here is based on the same eight factors (listed in the abstract). It looked to me like the figures for the high- and low-risk groups, or the high-, intermediate-, and low-risk groups were fairly close to the 2014 figures. However, this current research is based on 5,790 patients, nearly six times as many as in the earlier nomogram. As could be expected, that means the “confidence intervals” (CIs) around the median overall survival numbers are much tighter, meaning that the researchers are homing in on more precise estimates — tighter ranges for each number, and a lot more confidence in those ranges.
This abstract does not explain how to apply the nomogram. However, full details for the earlier, similarly structured nomogram are given in the 2014 paper linked above. I suspect the details for the new nomogram will be somewhat different when this update is formally published, but the nomogram scoring, etc., will probably be quite similar because the medians in this research and the 2014 research for the different risk groups have not changed by much. The 2014 paper explains that a main use of the nomogram is to aid stratification for randomization of patients in clinical trials.
Dear Jim:
I think you are misunderstanding this abstract. All that this abstract appears to me to do is revalidate the 2014 version of the Halabi nomogram. It doesn’t change it. The reason it doesn’t change it is that the data they used to revalidate the nomogram excluded trials of any drug or combination therapy that has shown a positive impact on outcomes of treatment of mCRPC.
Re: Halabi Nomogram update (Abstract #7 on the list)
Sitemaster: That’s the way I see this update also. By changes in the “details”, I just meant the exact cut-point values for each of the eight factors in the points table and the curves associated with the 18, 24, 30, 36, 48, and median survival months will almost certainly be slightly different than they were in Figure 2 in the 2014 paper.
It makes sense that the Hallabi nomogram would be used widely to stratify patients in Phase III trials for mCRPC treatments. Do you (or anyone) know whether that is the case?
I have no idea whether the Halabi nomogram is actually used in the the way that the authores suggest. What I do know is that I have never seen outcomes reported by Halabi risk levels.
Use of the Halabi Nomogram in Clinical Trial Planning
This continues the exchanges on the Halabi Nomogram. The bottom line for me is that I’m now more puzzled in how it is used in trial planning/reporting.
Building on Sitemaster’s 5/19/ 9:45 am response, I decided to take a look at protocols for clinical trials for metastatic CRPC as recorded at clinicaltrials.gov. I did a couple of searches to develop lists, and I looked at 13 trials, probably about half of those available that included a link to the trial protocol document; the list included pilot, Phase I, Phase II, and Phase III trials. I then searched those protocols (Ctrl-F) to find requirements to record the eight factors that are the basis for the Halabi nomogram.
What I found was that only two of the 13 trials required recording of all eight factors. Eight of the trials were missing only one factor, but that is all it takes to rule out use of the Halabi nomogram. Two more trials were missing only two of the 8, and one trial was missing four of the 8 factors.
The factors missing the most, at five each, were opioid use (searched for opioid, analgesic, and pain — with further checking — before ruling out), and LDH (lactose dehydrogenase). Hemoglobin was surprisingly missing three times (also checked CBC before ruling out), albumin twice (also checked CMP), and alkaline phosphatase once (also checked CMP). (I further checked for abbreviations.) There were no misses for disease site (as you would expect for a trial involving metastatic disease), ECOG performance status, or PSA (naturally!).
I’m really surprised that trials of men with metastatic disease were not interested in recording opioid use. Obviously my sample is quite small, but it suggests there isn’t much interest in the Halabi nomogram for planning/interpreting trials. It would be so simple to cover these extra bases. Thinking about my own labs, I am not asked about opioid use when I have one of my periodic oncology exams, but I fill out a pain scale, and I suspect I would get a follow-up question on analgesics if I indicated significant pain. Regarding other labs, I have been tested so often that the hematologist just looks at the needle and tells it “You know the drill” and the needle jumps by itself and sticks into a vein. These tests always include a CMP and CBC, and of course PSA, so albumin, alkaline phosphatase, hemoglobin and PSA are covered. My previous scans have my disease site status. That just leaves LDH and ECOG, with the latter easily assessed by a few questions.
My point is that it would be easy to add the missing data, and therefore, since the trialists have not seen fit to do so, it seems that the they are just not much interested in using the Halabi nomogram. That surprises me. I have heard Halabi nomogram comparisons used in an FDA Oncology Drug Advisory Committee hearing; I believe it was in support of Provenge.
Count me as puzzled.