A-DREAM/Alliance A032101 study presented by Dana-Farber Cancer Institute's Dr. Atish Choudhury shows 41% of favorable responders to testosterone suppression plus androgen receptor pathway inhibitor remaining treatment-free with testosterone recovery at 18 months after treatment interruption.
So I'm very excited to talk about our phase two trial of androgen deprivation therapy interruption in patients who are responding exceptionally to androgen receptor pathway inhibitors and metastatic hormone sensitive prostate cancer, also called a DREAM. This is an Alliance trial A032101. The background here is that patients who have metastatic prostate cancer are normally treated with testosterone lowering drugs, what we refer to as androgen deprivation therapy, in combination with second hormone drugs that block hormone signals within the cancer cells, and those are called androgen receptor pathway inhibitors. So, the way that those trials were done that demonstrated that, um, these combinations prolong survival in patients with metastatic prostate cancer, is that patients started these drugs. And stayed on them continuously ongoing for the rest of their life. And, uh, these drugs can be very, very effective in some patients and drive their PSA levels to, which is a marker of their cancer, to very low levels down to less than 0.2. And so, the question that we asked in the study is that if you have that kind of exceptional response, is there an opportunity to actually take breaks from treatment and show similar outcomes in terms of When your cancer actually becomes resistant to treatment. Um, so the way that this study was designed is that we just enrolled 75 patients across, uh, several sites called the National Clinical Trials Network. Uh, we enrolled patients who were on this combination for 18 to 24 months, and their PSA was less than 0.2 nanograms per milliliter, and just stopped the treatment and saw what happened over time. So, the PSA and testosterone levels were monitored every 3 months. These patients got scans every 6 months, and we actually asked questionnaires about their quality of life every 6 months as well. And the triggers to reinitiate treatment were a PSA above 5, radiographic changes that we could detect on the scans and prostate cancer-related symptoms. And the primary endpoint of the study is how many patients were able to remain off treatment for 18 months with just Testosterone recovery to greater than 150 nanograms per deciliter, with the idea that if your testosterone recovers above that range, that you can reverse many of the side effects of androgen deprivation. And we felt like 18 months was a pretty fair, um, off-treatment interval that would suggest some interest in moving forward with this idea. And if more than 30% of patients achieved this goal, then we could Move forward with further trials of the strategy to learn, um, who might have the most benefit here. So, the first question was, how many of the patients who stopped treatment actually were able to recover testosterone back above 150, and it was about 68% of patients, which is not everyone, but it is more than half of the patients, about 2/3. And what we found was that, Um, 32 of the 78 patients who enrolled on the trial, so 41% were actually able to recover their testosterone and remain treatment-free for 18 months. So it did meet its primary endpoint that more than 30% of patients were able to meet that threshold. What's particularly interesting is that we followed these patients for, on average, more than 2 years after they stopped treatment, and at 27 months of median follow-up, actually 30 of the 78 patients, or 38.5%, remain with no further treatment at all, which is more than what we expected. And what we found in terms of looking at patients, um, what predicted the time off treatment is that patients who had, um, higher volume disease at their initial diagnosis were more likely to have to resume treatment than patients with low volume disease, and patients who had radiation to the sites of metastases were less likely to have to resume treatment during the follow-up. Uh, in this time frame, 4 patients died, but actually only 1 of the deaths was from prostate cancer. The other 3 deaths were from myelodysplastic syndrome, influenza, and myocardial infarction, which really demonstrates that, uh, in this patient population, where the median age was about 70, there are many competing causes of death, and prostate cancer is only one of them. So our key takeaways here was that the study met its primary endpoint, with 41% of patients remaining treatment-free with testosterone recovery, 18 months after stopping treatment. 38.5% of patients continue on treatment interruption at 27 months of median follow-up, and only 1 of 4 deaths have been from prostate cancer. So we concluded that a treatment holiday in favorable responders is a reasonable consideration, and so optimal strategies for intermittent treatment, uh, warrant further study.
