One of the problems with clinical trials for late-stage prostate cancer today is that we commonly need to follow all patients until death before we can collect sufficiently accurate data to be certain that a particular product is or is not effective in extending patient survival.
A new paper by Armstrong et al. in the journal Urologic Oncology has now suggested that something known as a “bone scan index” or BSI may be an accurate surrogate for overall survival, and might therefore offer a way to reduce the time to completion of clinical trials of drugs being evaluated in late-stage disease. You can think of the BSI as a way to assess changes in bony disease burden in a consistent and quantitative manner.
The BSI was already known to have prognostic value in the management of prostate cancer. What Armstrong and his colleagues did was to use automated software to analyze the bone scans from a subset of the patients involved in a randomized, double-blind, Phase II clinical trial of a drug (tasquinimod) that is in development for the treatment of metastatic, castration-resistant prostate cancer (mCRPC), and compare the data on BSI levels to the data on overall survival among study participants. The initial results of this trial were first published back in 2011.
So, in the current paper, Armstrong et al. looked at the bone scans from patients enrolled in the trial, analyzed these bone scans using the automated software to calculate the individual BSIs for some of the patients, and then compared the patients’ BSI levels over time to other data being collected, including things like progression-free survival, overall survival, and whether the patients had been treated with tasquinimod or with a placebo.
Here is what they found:
- 201 men were enrolled in the trial altogether.
- Of those 201 men, 85 had bone scans of sufficient quality for analysis carried out at baseline (i.e., at entry into the trial) and at 12 weeks after initiation of treatment.
- 57 of these patients had been treated with tasquinimod.
- 28 of these patients had received a placebo.
- Baseline BSIs correlated with PSA levels and with alkaline phosphatase levels.
- Baseline BSIs were associated with overall survival
- On univariate analysis (hazard ratio [HR] = 1.42, P = 0.013) and
- On multivariate analysis (HR = 1.64, P < 0.001)
- On multivariate analysis, BSI worsening at 12 weeks was prognostic for
- Progression-free survival (HR = 2.14 per BSI doubling, P < 0.001)
- Overall survival (HR = 1.58 per BSI doubling, P = 0.033)
- Treatment with tasquinimod delayed BSI progression compared to treatment with a placebo.
It has already been reported, based on this trial, that treatment with tasquinimod increased median overall survival of trial participants by 3 months compared to treatment with a placebo.
Armstrong et al. conclude that:
- BSI and BSI changes over time were independently associated with overall survival in men with mCRPC.
- A prospective evaluation of BSI progression and response criteria in Phase III trials of men with mCRPC is warranted.
Now we do need to be clear that data like these from a relatively small subset of men in this Phase II trial are not definitive. What they do is they establish a testable hypothesis: that a delay in time to doubling of a patient’s BSI can be correlated to a delay in disease progression and an extension of overall survival.
We know that there is at least one ongoing Phase II trial today that is testing this hypothesis. We would hope that there are already plans in place to also test the hypothesis in a larger Phase III trial.