The 2013 Genitourinary ("2013 GU") Cancers Symposium, A Transformative Multidisciplinary Approach, to be held 14-16 February, 2013, includes multiple poster sessions on Dendreon's (DNDN) Provenge (sipuleucel-T) that will be of major interest to the medical community in general and practitioners treating prostate cancer in particular. Of particular interest are the results of the study Dendreon has been performing related to the sequencing of Provenge, its immunology treatment for asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer, and Johnson & Johnson's (JNJ) Zytiga. A high-level overview of Dendreon's presentations is provided below.
Abstract #30: Real-world experience with sipuleucel-T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel (D): Data from PROCEED. (C3)
A. Oliver Sartor - Tulane Cancer Center
By September 2012, of 560 patients in the PROCEED trial (Clinical trial information: NCT01306890) who completed treatment with sipuleucel-T (Provenge), 15% had previously received docetaxel (Taxotere). The general conclusion that could be drawn was that Provenge product parameters were comparable regardless of prior D exposure.
Abstract #34: Randomized phase II trial evaluating the optimal sequencing of sipuleucel-T and androgen-deprivation therapy (ADT) in patients (pts) with biochemically recurrent prostate cancer (BRPC). (C7)
Emmanuel S. Antonarakis - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
In this Phase 2 study (Clinical trial information: NCT01431391), men were equally randomized to Arm 1: sipuleucel-T followed by ADT (started 2 weeks after the final sipuleucel-T infusion); or Arm 2: ADT followed by sipuleucel-T (started after 3 months of ADT). The primary endpoint was antigen-specific immune responses. Based on the work to date, there were no differences between the arms in cellular or humoral immune responses.
Abstract #40: Changes in circulating tumor cells (CTC) and markers of inflammation after sipuleucel-T treatment. (C13)
Mehmet Hepgur - University of Southern California, Norris Comprehensive Cancer Center
The investigators prospectively collected CTC, LDH, and inflammatory markers as part of an audit to investigate changes after sipuleucel-T treatment compared to baseline. Men with CRPC had blood drawn routinely before and after treatment with Provenge. Conclusions: "We found that CTC counts can decline after (Provenge) treatment, including conversion from unfavorable to favorable range, and can change independently of PSA. Correlation of CTCs with outcomes in a prospective study is warranted to explore this as a potential biomarker."
Abstract #74: Relationship of sipuleucel-T with time to first use of opioid analgesics (TFOA) in patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) on the IMPACT trial. (E11)
Eric Jay Small - Helen Diller Family Comprehensive Cancer Center, University of California
This presentation, based on a retrospective analysis of the IMPACT trial (Clinical trial information: NCT00065442), analyzed TFOA using a Cox regression model with adjustment for baseline PSA and LDH. It was concluded that relative to placebo, Provenge delayed the TFOA in patients with asymptomatic or minimally symptomatic mCRPC.
Abstract #114: A randomized phase II, open-label study of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) in metastatic castrate-resistant prostate cancer (mCRPC). (G15)
Eric Jay Small - University of California, San Francisco
Of all the abstracts, I must admit this was the first to which I turned. The question of sequencing sipuleucel-T (Provenge) and abiraterone acetate (Zytiga) has long been debated. The concern with the timing of these two treatments has to do with a number of factors, not the least of which is the patient's disease load, the rate at which his disease is progressing, and the fact that Zytiga must be co-administered with prednisone, which suppresses the immune system. Earlier, the Journal of Clinical Oncology had weighed in as follows:
"The practical dilemma of the appropriate sequence of use of the two new noncytotoxic agents (sipuleucel-T and abiraterone) is being addressed by trials that are under development. For now, given the broader window of applicability of abiraterone and the longer time required to develop an immune response with sipuleucel-T, if both agents are to be used, it seems reasonable to administer sipuleucel-T first with Abiraterone after additional disease progression. Biomarkers to help define the optimal use of immunotherapy are needed."
Now, with the trial conducted by Dendreon (Clinical trial information: NCT01487863), we have our first objective "look" at how the two treatments work together synergistically…or not. I suggest you read the abstract to gain an understanding of the trial protocols. Basically, a two-part study of Provenge was undertaken using (A) concurrent or (B) sequential Zytiga plus prednisone. In both cases, patients had asymptomatic or minimally symptomatic mCRPC. The primary endpoint was cumulative CD54 upregulation (measure of antigen presenting cell activation). The results for twenty-nine patients are reported, 16 in the concurrent arm and 13 in the sequential arm . In what many might find surprising, Provenge's product potency and prime boost, when administered with Zytiga, were similar to that observed when Provenge was administered by itself.
Abstract #131: Real-world experience with sipuleucel-T in patients (pts) ≥80 years old with metastatic castration-resistant prostate cancer (mCRPC): Data from PROCEED. (H14)
Chadi Nabhan - Oncology Specialists SC, Lutheran General Hospital
Using data from the PROCEED trial (Clinical trial information: NCT01306890), the intent of the effort reported was to understand the disease characteristics and product parameters in patients 80 years of age and older, given the high prevalence of mCRPC in that population. Of the 560 patients who completed Provenge treatment in the PROCEED trial, 20% were 80 or older. Upon detailing their disease characteristics, it was found that their product parameters were similar to those for their younger counterparts. The authors intended to follow-up the study reported by exploring overall survival data and correlations with immune parameters in both groups.
Abstract #147: P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation. (J12)
Tomasz M. Beer - Oregon Health and Science University, Knight Cancer Institute
This paper describes an evaluation of APC activation in patients who had been retreated with Provenge after progressing to mCRPC. As of September 7, 2012, seven patients had enrolled and received an infusion of Provenge. The median interval between the last infusion in the PROTECT trial and the first infusion in the trial reported was 8.6 years. The results demonstrated a higher-fold changed in the CD54 expression in the first retreatment compared with the initial infusion in PROTECT. These data are consistent with the presence of an immunological memory response to the immunizing antigen years after initial treatment. (Clinical trial information: NCT01338012)
Abstract #148: Immune response with sipuleucel-T in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Phase II ProACT study. (J13)
Thomas A. Gardner - Simon Cancer Center, Indiana University
Sipuleucel-T prepared using 10μg/mL PA2024 (PAP-GM-CSF antigen) stimulates immune responses and prolongs overall survival (OS). ProACT is an ongoing phase 2 study to evaluate immune responses and OS of sipuleucel-T when manufactured using 3 different concentrations of PA2024. (Clinical trial information: NCT00715078). At month 2, median serum anti-PA2024 and anti-PAP titers (IgG and IgM combined) were 128 and 32-fold higher vs. baseline respectively, compared to median serum anti-GM-CSF titers, which were 16-fold higher vs. baseline. Median serum anti-PA2024 titers (IgG and IgM combined) were significantly higher than those for anti-GM-CSF (p<0.001) at all timepoints and correlated with anti-PAP titers (r=0.840). PA2024 and PAP responder frequencies (IgG and IgM titers combined >12,800) were 79% and 47% of pts, respectively. Additional results will be published when available.
While all of the abstracts described above represent significant contributions to the scientific and medical literature, the two I would expect to generate the most interest among physicians, patients, and investors alike are (1) Hepgur's presentation on circulating tumor cells (Abstract #40), which suggested that the correlation of CTCs with outcomes in a prospective study is warranted iin order to explore this as a potential biomarker, and (2) Antonarakis's presentation describing the sequencing of sipuleucel-T (Provenge) and abiraterone acetate (Zytiga) (Abstract #114), which suggests the order of treatment is not important.
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Additional disclosure: I am long DNDN and the May 2013 $3 PUTs. I am not a registered investment advisor and do not provide specific investment advice. The information contained herein is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. It is up to investors to make the correct decision after necessary research. Investing includes risks, including loss of principal.
Disclosure: I am long DNDN.