With the publication of data about enzalutamide in the New England Journal of Medicine last week, Professor Alan Ashworth, the head of the Institute for Cancer Research (ICR) in the UK, proclaimed “a golden age in prostate cancer drug discovery.”
Prof. Ashworth’s enthusiasm is certainly understandable. No one is going to disagree with him that great progress has been made in the potential to treat progressive forms of prostate cancer in the past few years:
- In April 2010, sipuleucel-T became the first form of personalized immunotherapy ever to extend overall survival in cancer (for men with asymptomatic or minimally symptomatic CRPC — metastatic or non-metastatic).
- Cabazitaxel — a taxane-based chemotherapeutic agent — used in combination with prednisone was approved (in June 2010) to extend overall survival in men with metastatic, castration-resistant prostate cancer (mCRPC) progressing after docetaxel-based chemotherapy.
- Abiraterone acetate + prednisone initially showed an overall survival benefit in men with mCRPC after docetaxel-based chemotherapy (and was approved for that use in April 2011) and — more recently — has shown a progression-free survival benefit in chemotherapy-naive men with asymptomatic or minimally symptomatic mCRPC.
- Radium-223 is the first injectable form of radiation therapy to demonstrate an overall survival benefit in any form of cancer (specifically in men with mCRPC who had or had not received prior chemotherapy).
- Enzalutamide (formerly known as MDV3100) has demonstrated an overall survival benefit in men with mCRPC after docetaxel-based chemotherapy and is still expected to demonstrate an overall survival benefit in chemotherapy-naive men with asymptomatic or minimally symptomatic mCRPC.
However, among these five new agents, the longest median overall survival benefit is still “only” 4.8 months (demonstrated by men in the enzalutamide trial). In that trial, the median age of the 800 men randomized to receive active drug was 69 years (range 41 to 92 years). Thus, the average extension of life of these patients was actually
4.8/(69 x 12) x 100 = 0.58 percent
The way that The “New” Prostate Cancer InfoLink looks at the progress made over the past 5 years or so is not so much as “a golden age” in prostate cancer drug discovery as it is a platform for real hope that such a golden age may be coming.
For us, that “golden age” will only begin when new forms of therapy start to show a median survival benefit that extends life by at least a year in men with mCRPC. In the enzalutamide trial mentioned above, a median overall survival benefit of a single year would have equated to a 1.45 percent extension in the overall life of the men on active drug. However, very few forms of cancer therapy have ever demonstrated a median overall survival benefit of a year for people with advanced, metastatic disease, so this would be a really meaningful change in the opportunity available to patients — especially if that benefit was shown by a form of therapy that had the potential to be used much earlier in the progression of the disease (and therefore to induce a far greater survival in less sick and much younger patients).
At present, we know of just one agent in advanced clinical trials that might even begin to approach this type of overall survival benefit — the immunotherapeutic agent Prostvac VF, which, in a randomized Phase II clinical trial, showed an overall survival benefit of 8.2 months. However, overall survival was not the primary endpoint of the trial in question, and so this result needs to be treated with great caution.
Of course the true “golden age” for research into treatment of prostate cancer will only begin if we can start to find ways to absolutely stop progressive prostate cancer in its tracks, without most of the side effects historically associated with things like surgery and radiation therapy. However, when we consider the progress made over the past 5 to 10 years, even that golden age may be closer than we could possibly have believed just 20 years ago.