Immunotherapy has a major and expanding role in the treatment of cancer, including advanced prostate cancer. Over time there have been a number of naysayers as the immunotherapy Provenge has played the role whipping boy by critics. The common criticism leveled at Provenge can be summed up simply, “It doesn’t work.”
The plain truth is that this criticism is not true. Provenge does extend life, but it does not affect a man’s PSA nor does it affect radiologic progression. However, it does extend life, the most important factor for us with advanced prostate cancer.
Why is Provenge (and immunotherapy) not provided it proper acknowledgment? It is money. Provenge consists of three separate treatments at a total cost that is in excess of $105,000. From a statistical analysis you could say that each month of additional survival costs (4.1 months based on the IMPACT Trial) approximately $25,000.
Each of us needs to decide the morality of this price tag, but newer immunotherapies are performing better (longer survival extension) at hopefully will come to market at a cheaper cost. Ipilimumab (Yervoy) has been approved for the treatment of metastatic Melanoma and Prostvac is in the middle of its phase 3 trials (phase 1 and 2 trials all demonstrated a significant survival advantage) for men with advanced prostate cancer.
It is now time for the naysayers to drop the anti-immunotherapy attitude. It extends life and does it with out many of the extreme side effects we experience from both the hormonal therapies as well as the toxic chemotherapies. Evidence strongly suggests that immunotherapy will play an important role in treating prostate cancer as well as many other cancers.
Preliminary results have shown that Prostvac vaccine with ipilimumab ¬(Yervoy) boosts overall survival in men with castration-resistant prostate cancer.(1)
Two previous phase II trials looked at Provenge alone and found an overall survival benefit in men with metastatic castration-resistant prostate cancer. The first trial, which included 125 men, found a median overall survival of 25.1 months. The second trial, which included 32 men, showed a median overall survival of 26.6 months. Both trials demonstrated improved overall survival over that predicted by the Halabi nomogram (a model that uses historical data to estimate survival of prostate cancer patients after castration): The first study showed an 8.5-month improvement in median overall survival, and the second had a similar 9.1-month improvement in median overall survival compared with predicted survival.
At the recent ASCO GU meeting there was additional data presented on a phase 1 trial of 30 men with metastatic castration-resistant prostate cancer (and baseline characteristics similar to those in the phase II trials) treated with the combination of Prostvac plus escalating doses of ipilimumab. Follow-up was about 80 months.
The predicted survival of chemotherapy-naive patients with metastatic castration-resistant prostate cancer is 18.5 months on the Halabi nomogram. The updated overall survival analysis showed a median overall survival of 31.3 months using the intensified immunotherapy approach.
The most impressive results were seen in the group receiving the highest dose of ipilimumab (10 mg/kg) plus the vaccine: a median overall survival of 37.2 months. Additionally, it was disclosed that there is a major tail in the survival curve of this trial. About 20% of the men on the highest dose of ipilimumab are still alive at 80 months.
It is time for all of us to acknowledge the future role of immunotherapy in the treatment of advanced prostate cancer. We all owe a major debt to Provenge as it opened the possibility of using immunotherapy to successful extend our life.
1. Singh H, Madan RA, Dahut WL, et al: Combining active immunotherapy and immune checkpoint inhibitors in prostate cancer. 2015 Genitourinary Cancers Symposium. Abstract 172. Presented February 26, 2015.
Joel T Nowak, M.A., M.S.W.