So … what IS going to be “hot” at ASCO this year?

It appears that when it comes to the new data to be presented at ASCO this year, this will be the first time for several years that we don’t see some really groundbreaking new data from a large Phase III trial of some new form of therapy at one of the major meetings. But there is a lot of detail and a lot of information about new trials in development.

There seem to be about 200 to 250 abstracts being presented on prostate cancer at the ASCO annual meeting this year. Over the next couple of weeks we shall be trying fill readers in on what really does look interesting from the various presentations. And in fact we can start with data from one study that has considerable long-term implications for the conduct of clinical trials of new therapies in early stage prostate cancer patients (who may take decades to reach currently meaningful trial endpoints such as metastasis-free survival, let alone prostate cancer-specific or overall mortality).

Sweeney at al. (see abstract no. 5023) will be reporting initial data from a study conducted by the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) Working Group. Their goal is to try to find meaningful and accurate surrogate endpoints for the conduct of clinical trials in patients with localized forms of prostate cancer, and they decided that disease-free survival (DFS) could well be a surrogate for overall survival (OS).

They therefore set out to identify eligible randomized trials (either completed or currently ongoing) designed to compare differing forms of treatment in men with localized prostate cancer — with the goal of collecting and analyzing de-identified individual patient data from the trial managers of each such trial. They were able to identify 102 such clinical trials.

The research team defined DFS as time from randomization into any of the trials to the first evidence of clinical recurrence (loco-regional or distant) or death from any cause. OS was defined as the time from randomization to death from any cause. They then set out to evaluate

  • Whether DFS was an effective surrogate for OS
  • Whether time to disease recurrence (TDR) was an effective surrogate for prostate cancer-specific, i.e., disease-specific survival (DSS)

Here are the study results currently available (as of January 2016):

  • Individual patient data were available for analysis from 16,999 men randomized to any one of 20 mature trials.
  • 32 percent of the data came from men enrolled in trials involving radical prostatectomy.
  • About 30 percent of the patients had intermediate-risk disease.
  • About 50 percent of the patients had high-risk disease.
  • 86 percent of the patients were < 74 years of age.
  • At an average (median) follow-up of 10.2 years,
    • 5,370/16,999 trial participants (32 percent) had died.
    • 1,592/5,370 trial participants who had died had died of prostate cancer.

Sweeney et al. conclude that, based on the data shown in the table associated with their abstract, that

  • DFS can be used as a surrogate for OS.
  • TDR can be used as a surrogate for DSS.

Now these data will need to be substantiated using other data from other trials before we can simply assume that Sweeney and his colleagues are correct, but if they can be shown to be correct, and (for example) DFS really is a good quality surrogate endpoint for overall survival, then the conduct of high-quality Phase III clinical trials in men with early stage forms of prostate cancer may become a real possibility; that could lead to approval of drugs and other forms of intervention in the management of early stage prostate cancer — and that might be a very big deal indeed!

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