Sipuleucel-T Studies Support Earlier Use, Reveal Potential Biomarker

Douglas McNeel, MD, PhD

The approval of sipuleucel-T (Provenge) in 2010 represented a major step in the development of cancer therapies, as it was the first autologous cellular immunotherapy approved by the FDA to treat any type of cancer. Currently, the vaccine is only approved to treat asymptomatic or minimally symptomatic metastatic castrationresistant prostate cancer (mCRPC). Research presented at ASCO 2012 examined the expanded use of sipuleucel-T, as well as methods to determine which patients might benefit the most from the therapy.

Four of the studies presented at ASCO that focused on sipuleucel-T yielded the following findings:

• An exploratory analysis of patient data from the phase III IMPACT trial—the study that led to approval of sipuleucel-T by demonstrating an improvement in overall survival—found that patients who had prognostic features indicative of less advanced disease, such as lower baseline prostate-specific antigen (PSA), lower baseline LDH, and an ECOG performance status score of 0, trended toward a more pronounced treatment response, suggesting that earlier administration of sipuleucel-T in patients with mCRPC may result in better survival outcomes.¹
• An increased count of eosinophil granulocytes— a type of white blood cell that becomes active when a patient has certain medical conditions or allergic reactions—could serve as a biomarker to determine response to sipuleucel- T. A retrospective analysis of data from three studies (D9901, D9902A, and IMPACT) found that increased eosinophil counts were seen in patients who received sipuleucel-T by their sixth week of treatment.² Those levels returned to near baseline by week 14 of the treatment. Patients with eosinophilia had better prostate cancer—specific survival (hazard ratio [HR] = 0.713; 95% CI, 0.525-0.970; P = .031) and better overall survival (HR = 0.753; 95% CI, 0.563- 1.008; P = .057) than patients without eosinophilia. Although the analysis was retrospective, Douglas McNeel, MD, PhD, a genitourinary oncologist with the University of Wisconsin School of Medicine and Public Health, Madison, said eosinophil count might be something that oncologists prescribing sipuleucel-T might want to monitor through routine blood analysis. “I think it may be of interest for them to look for this,” McNeel said. “It might at least be encouraging to point out to patients that they’ve indeed gotten a kind of immune response and that this may be associated with some benefit.”
• The open-label, phase II NeoACT study explored the delivery of sipuleucel-T in the neoadjuvant setting in patients with localized prostate cancer. In the trial, patients received sipuleucel-T prior to a radical prostatectomy. In an evaluation of immune activation in patients in the NeoACT trial, researchers found that “neoadjuvant sipuleucel-T [resulted] in robust immune system activation that included antigen presenting cells, memory and activated mature B cells, and both CD4-positive and CD8-positive T cells.” ³ The authors further noted that the cytokine profile suggests T cell activation without enhanced regulatory T cell functionality. All of this evidence suggests that neoadjuvant delivery of sipuleucel-T is associated with a good immune response.
• An additional analysis based on the NeoACT study examined the ability of sipuleucel-T to induce T cells to infiltrate the tumor site.⁴ Researchers observed a greater than ≥3-fold increase in mean total T cells (CD3-positive), T helper cells (CD3-positive/CD4-positive), and cytotoxic T cells (CD3-positive/CD8-positive) at the radical prostatectomy tumor interface compared with levels of those T cells from the biopsy, radical prostatectomy tumor, and radical prostatectomy benign tumor. The researchers posit that based on these data, sipuleucel-T is able to modulate the presence of lymphocytes in prostate cancer tissue in vivo. Chodak G, Schellhammer PF, Whitmore JB, et al. Overall survival (OS) benefit with sipuleucel-T by baseline PSA: An exploratory analysis from the Phase 3 IMPACT trial. J Clin Oncol. 2012;30(suppl; abstr 4648). McNeel DG, Lin DW, Gardner T, et al. Correlation of increased eosinophil count following sipuleucel-T treatment with outcomes in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC). J Clin Oncol. 2012;30(suppl; abstr 4650). Sheikh NA, Wesley JD, Perdue N, et al. Evaluation of immune activation following neoadjuvant sipuleucel-T in subjects with localized prostate cancer. J Clin Oncol. 2012;30(suppl; abstr 2563). Fong L, Weinberg VK, Chan SE, et al. Neoadjuvant sipuleucel-T in localized prostate cancer: Effects on immune cells within the prostate tumor microenvironment. J Clin Oncol. 2012;30(suppl; abstr 2564).