Sipuleucel-T Stimulates Response in Localized Setting, Study Finds

Leonard G. Gomella, MD

The Bernard W. Godwin Jr. Professor of Prostate Cancer Chairman, Department of Urology Director, Clinical Affairs Kimmel Cancer Center Thomas Jefferson University Philadelphia, PA

The neoadjuvant administration of sipuleucel-T (Provenge) may stimulate an immune response in patients with localized prostate cancer without adversely affecting their surgeries, according to study results presented at the 2012 Genitourinary Cancers Symposium. The study explored the possibility of using the vaccine earlier in the treatment timeline than its current approved indication for patients with asymptomatic or minimally symptomatic metastatic castrationresistant prostate cancer.

In a phase II trial, 42 patients with localized prostate cancer who were slated for radical prostatectomy were given sipuleucel-T in three infusions administered 6 to 7 weeks prior to their surgeries. Prostate cell specimens were collected prior to and following treatment with sipuleucel-T. Patients were followed for 72 weeks, and also randomly assigned to receive a booster treatment with the vaccine or no further treatment.

At the time of the presentation in February, immunohistochemistry analysis had been completed on 19 patients. “Significant increases (>2‑fold) in CD3- positive and CD4-positive T-cell populations were observed at the tumor rim, where benign and malignant glands interface, compared with the pretreatment biopsy,” researchers said in their abstract. Surgical impact was measured by operative complications, procedure time, and estimated blood loss.

In a companion abstract, investigators reported a “robust immune system activation,” including antigen-presenting cells and memory and activated mature B cells.

Although the results are preliminary, the study suggests more work should be done to explore the potential benefits in patients who have an earlierstage prostate cancer, according to Leonard G. Gomella, MD, who served as chair of the conference program committee at the American Society of Clinical Oncology symposium.

“This is very exciting because if immunotherapies work, they tend to work when there’s a minimal amount of disease,” Gomella said.

He also said the study found tumor markers through which the impact of the treatment could be evaluated.

“One of the challenges that we have when we look at all immunotherapy, and particularly when we look at the sipuleucel-T immunotherapies, is that we don’t have a specific marker for response,” Gomella said. “This is very encouraging and very positive news that this study was able to show that there were specific markers of an immune response in the prostate.”

He noted that the study is among early-phase investigations into stimulating the immune cells in the preprostatecomy setting, but that major clinical trials are “a long way off.”

Investigators said in their abstract that “work is ongoing to more fully characterize the immune response within the prostate tumor tissue and in the peripheral blood.”

Fong L, Weinberg VK, Corman JM, et al. Immune responses in prostate tumor tissue following neoadjuvant sipuleucel-T in patients with localized prostate cancer. J Clin Oncol. 2012;30:(suppl 5). Abstr 181.

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 5). Abstr 178.