Immunotherapy for Castration-Resistant Prostate Cancer: A New Era?

Sipuleucel-T demonstrated a survival advantage over placebo in men with metastatic CRPC who had few or no symptoms.

Men with metastatic castration-resistant prostate cancer (CRPC) typically survive about 1 to 2 years after progression on hormonal therapy. Until 2010, only one chemotherapy drug — docetaxel — had been shown to prolong the survival of these patients (by about 2 to 3 months) when used with prednisone (JW Oncol Hematol Feb 5 2008). The rationale for developing cancer immunotherapy — to eradicate cancer cells — has always been strong. However, finding an effective immunotherapy has not been easy.

In April 2010, the FDA approved a therapeutic cancer vaccine called sipuleucel-T (Provenge). This agent uses dendritic cells specific to an antigen, prostatic acid phosphatase (PAP), which is fused to granulocyte–macrophage colony-stimulating factor. Because PAP is expressed on most prostate cancer cells and is relatively specific to prostate epithelium, it represents an attractive target for immunotherapy. Sipuleucel-T is an autologous therapy: Patients are leukopheresed, their dendritic cells are pulsed ex vivo with the PAP fusion protein, and the altered cells are then reinfused into the patient.

Now, we have published data from IMPACT, the largest of three trials that led to the FDA approval of sipuleucel-T. In this phase-III trial, 512 asymptomatic or minimally symptomatic men with metastatic CRPC were randomized, in a 2:1 ratio, to receive sipuleucel-T or a placebo intervention. Treatment was administered every 2 weeks, until a total of three doses had been given. Median follow-up was 34 months. Overall survival was significantly longer in the sipuleucel-T group than in the placebo group (25.8 months vs. 21.7 months; adjusted hazard ratio for death, 0.78; P=0.03). The two groups did not differ significantly in time to disease progression or response to therapy. The most common toxicities of sipuleucel-T were mild chills, fever, and headache.


Citation(s):

Kantoff PW et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010 Jul 29; 363:411.

Longo DL. New therapies for castration-resistant prostate cancer. N Engl J Med 2010 Jul 29; 363:479.