An update on potential treatment options for men with non-metastatic, hormone resistant prostate cancer
Over the last few years, there’ve been a slew of clinical trials investigating new treatments, combinations and sequences for men with hormone sensitive disease that has, and hasn’t, spread outside the prostate; and for men with hormone resistant metastatic disease. However, there have been very few breakthroughs for men with hormone resistant disease that hasn’t yet spread outside the prostate.
Part of the problem is that this is a small and hard to define patient population. At the moment, we believe that there are around 4,000 men in the UK who fit into this category, but we expect this number to decline as imaging improves, and it becomes possible to detect distant metastases that have previously remained undiagnosed.
At the moment, men in this disease category have no effective treatment options until their cancer progresses, when they will become eligible for treatments approved for metastatic, hormone resistant disease. Current best practice for these men is to continue hormone therapy (despite the onset of resistance) and monitor for progression to advanced disease.
However, two recent trials have investigated the possibility of treating these men with second line hormone therapies that have already been studied, and in the case of enzalutamide approved, in the metastatic hormone resistant disease setting.
Both PROSPER and SPARTAN reported positive results. In these trials, the researchers found that men with hormone resistant disease that hasn’t yet spread responded well to both enzalutamide and apalutamide respectively.
Both treatments, enzalutamide and apalutamide, looked at men with ‘high-risk’ or ‘high-volume’ non metastatic, hormone resistant prostate cancer, which they defined as men whose PSA has doubled in 10 months or less. Both treatments gave these men around 23 months’ delay in their prostate cancer progression, which can consequently delay symptoms and help men live longer.
NICE has already considered the cost-effectiveness of enzalutamide in the non-metastatic, hormone resistant setting, and decided that it shouldn’t be routinely recommended. Although the treatment resulted in progression-free survival, the overall survival data suggested that the benefit of enzalutamide to the patient wasn’t significant enough to outweigh the cost. The Scottish Medicines Consortium will consider enzalutamide for this patient population in September.
The SPARTAN trial for apalutamide has not yet collected overall survival data, so NICE will consider this treatment for non-metastatic, hormone resistant disease for the first time in September 2019.
The key question, in light of the NHS’ ‘single novel treatment’ policy, will be: if each man can only have one of enzalutamide, abiraterone or apalutamide and any stage of disease, how do we decide which men will benefit most from each treatment, and when?
As research continues, we hope PROSPER and SPARTAN will shed some light on this.
This question forms a key research priority for us, and will be addressed as part of our precision medicine programme; two major awards focused on finding the right treatment for each man in both hormone sensitive and hormone resistant disease.