Use of neoadjuvant sipuleucel-T (Provenge) engendered an immune response in men with early-stage prostate cancer slated for radical prostatectomy (RP), according to a study presented at a poster session at the 2012 American Society of Clinical Oncology Genitourinary Cancers Symposium held in San Francisco, California. The vaccine is approved by the US Food and Drug Administration in the setting of rising prostate-specific antigen (PSA) level in metastatic castration-resistant prostate cancer, and this study suggests that it may be beneficial when used up front. Large randomized trials of sipuleucel-T at earlier stages of disease are ongoing.
“This is an off-label use of sipuleucel- T. We wanted to see if we could induce an immune response similar to what we induce in castration-resistant prostate cancer when given earlier in the course of disease. We also wanted to assess its safety in this setting. The data suggest that sipuleucel-T may modulate the presence of lymphocytes at the prostate tumor site,” said lead author Lawrence Fong, MD, UCSF Comprehensive Cancer Center, San Francisco, California.
The tissue-based study included 40 patients with early prostate cancer slated to undergo RP. Median age was 61 years, and 98% were Caucasian. Patients were treated with 3 planned infusions of sipuleucel-T at approximately 2-week intervals, beginning 6 to 7 weeks prior to planned RP.
Immunohistochemistry (IHC) to measure immune cell response was performed on tissue from pre-RP biopsies and on the prostatectomy specimen following sipuleucel-T treatment. Patients were followed for 72 weeks post-RP for safety and immune responses.
Thirty-eight of 42 patients (90%) received all 3 preoperative infusions of the vaccine; 3 received 2 infusions, and 1 received 0 infusions. IHC analysis was completed on 25 patients for CD3 and CD8 expression and on 23 for CD4 and FOXP3 expression.
A greater than 3-fold increase was observed in mean CD3+ and CD3+/CD4+ cells per area as well as 2- to 3-fold increase in CD3+/CD8+ cells/area at the RP interface compared with pretreatment biopsy, RP tumor, and benign tissue. Regulatory T cells (CD3+/CD4+/FOXP3+ cells) were also increased at the tumor interface but represent a small population of the observed T cells.
On day 1 following pre-RP sipuleucel- T infusion, the following adverse events were reported in >5% of patients: fatigue (36%), headache (17%), myalgia (12%), arthralgia (10%), and chills (7%). One serious adverse event (infusion-related reaction) was reported. There did not appear to be any impact of sipuleucel- T on surgery, Fong said.
Nicholas Vogelzang, MD, Chair and Medical Director of the Developmental Therapeutics Committee of US Oncology, said this abstract was important. “The myth has been that sipuleucel-T is not a good immunotherapy and that we are not able to measure its effect on tumor. Yet we use other therapies in cancer that extend progression-free survival without being able to show an effect on the tumor. This abstract showed at a cellular level that immune cells are penetrating into cancer, providing proof of principle for studying it earlier in the disease.”
A study is now under way in patients with rising PSA after RP or radiotherapy, comparing sipuleucel-T given before or after hormone therapy.
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