Sequencing of the various new advanced prostate cancer treatments remains a hot topic in our community. What treatment should come first and will the combination of various treatments be even more effective? These types of questions are constantly buzzing around us and they will continue to as long as we develop new treatments.
The only way to begin to answer these questions is through our continuing to have clinical trials evaluating these questions. In a paper due to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Dr. Antonarakis et al. will share one such trial using ADT and sipuleucel-T (Provenge).
Provenge is currently approved only for the treatment of asymptomatic and minimally symptomatic, metastatic, castration-resistant prostate cancer (mCRPC). There have been many people who have asked why not use Provenge earlier, even before the development of castrate resistance? We know that men who do best with Provenge are those who have the lowest PSA when they receive the treatment. Could earlier use of Provenge yield even better survival?
The paper, “A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): immune results” begins to answer this question. The paper asks if a man with biochemically recurrent disease and who is considered at high risk to develop metastasis would do better if he were treated first with Provenge and then have hormone therapy (ADT) added or first have ADT for a short time and then ass Provenge.
The trial that looked at this question, the STAND trial, was a phase II trial that randomized 68 men with biochemical recurrence (PSA recurrence only). The trial had two arms; One arm that first gave the 3 infusions of Provenge, then added ADT 2 weeks after the last Provenge infusion and the other arm gave three months of ADT, then Provenge with an additional 9 months of ADT. Each arm had 34 men.
ADT consisted of 45 mg leuprolide s.q. at 6-month intervals. The primary endpoint of the study is cellular immune response to treatment. Secondary endpoints are hormonal and cytokine responses, product parameters, and safety.
The results, which are preliminary, due to be presented are:
1- Higher levels of serum cytokines were observed in men in Arm 2 as compared to Arm 1.
2- The pattern of these serum cytokines suggests a mixed TH1/TH2 cellular immune response.
3- Elevations were observed in the TH1 (IFN?, IL-12), TH2 (IL-4, IL-5, IL-10, IL-13) and TH17 (IL-17) subsets (all P < 0.05). 4- The increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT immune responses 2 weeks after the third sipuleucel-T infusion in Arm 2 vs. Arm 1 (40.5 vs. 12.8 spots; P = 0.086). 5- Antigen-specific hormonal responses were induced in both arms of the trial with no differences yet observed between the arms.So, what does this actually mean? According to Dr. Antonarakis, “these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation.” He also noted that, while this data will require further confirmation, “they are consistent with preclinical studies showing that ADT enhances T-cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity.”It is important to note that this is preliminary data from a very small study. Despite our desire to draw great inferences and rush out to try and get Provenge immediately upon a biochemical recurrence we do not know that this better response will actually correlate with future clinical results. We also do not know if there is any argument to have Provenge prior to a biochemical recurrence, or while one remains hormone responsive. These answers will come only with further trials.I applaud and am happy that Dendreon continues to perform these trials and urge that they find the means to even further expand the trials to answer these most important questions.Joel T. Nowak, M.A., M.S.W.Don't forget to go to www.StartACure.com and support prostate cancer research, even with $1.00.