Download File - JOHN J. HADDAD, Ph.D.

74 Teofilovici and Wentworth
Liponova completed a phase 3 trial of Reniale, involving 558 patients with
nonmetastatic RCC. Although the majority of clinical research indicates greater
benefit of cancer vaccines among patients with earlier-stage disease, a subset
analysis of the phase 3 trial found a significant reduction in tumor progression
for patients with T3 tumors but not those with T2 tumors (21). Five-year progression-free
survival (PFS) was 81.3% for patients with T2 tumors who
received vaccine (n ¼ 119) versus 74.6% for similar patients in the control arm
(n ¼ 145; P ¼ 0.216). For patients with T3 tumors, five-year PFS was 67.5% for
those in the vaccine arm (n ¼ 58) compared with 49.7% for those in the control
arm (n ¼ 57; P ¼ 0.039). Liponova provided an updated report with additional
OS data (22). This secondary intent-to-treat (ITT) analysis was performed on
477 patients (233 patients in the treatment group and 244 patients in the control
group). PFS remained in favor of the Reniale group (P ¼ 0.0476, log-rank test),
with no statistically significant OS difference between both groups. In the
per protocol group, there remained 134 patients in the Reniale group and
218 patients in the control group where both PFS and OS were statistically
significant in favor of the Reniale group (P ¼ 0.024, log-rank test, for PFS; and
P ¼ 0.0356, log-rank test, for OS, respectively).
Provenge 1 (Sipuleucel-T; Dendreon, Seattle, WA, U.S.)
Provenge consists of autologous (patient-derived) DC that have been cultured with
a “delivery cassette” that contains a version of the prostate cancer–associated
antigen prostatic acid phosphatase (PAP) (found in about 95% of prostate cancers)
and the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). It
is designed to activate specialized immune cells called T cells to recognize and
destroy cells bearing the PAP antigen. In contrast to personalized vaccines using
patient’s own tumor to derive a large repertoire of antigens, Provenge uses a
generic antigen common in prostate carcinoma. A phase 3 trial of Provenge
involving 127 patients with asymptomatic, androgen-independent, metastatic
prostate cancer (study D9901) missed the primary end point of time to progression.
However, the final three-year follow-up data showed a median survival benefit of
21%, or 4.5 months, and a threefold improvement in survival at 36 months
compared with placebo, regardless of Gleason score (P ¼ 0.010; HR ¼ 1.7) (23).
A second phase 3 trial (study D9902A), involving 98 men with asymptomatic,
metastatic, androgen-independent prostate cancer, corroborated findings
from the first trial: Patients who received vaccine had a 19.0-month median survival
time compared with 15.7 months for patients who received placebo, representing
a 21% improvement (P ¼ 0.331; HR ¼ 1.3). Integrated analysis of data
from both trials showed a statistically significant survival benefit among the overall
ITT population of 225 patients: Patients who received Provenge had a median
survival of 23.2 months compared with 18.9 months for patients who received
placebo (P ¼ 0.011; HR ¼ 1.5) (24). A third, pivotal phase 3 trial (study D9902B)
is ongoing to evaluate Provenge as a treatment for advanced prostate cancer.