Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer

被引:859
作者
Small, Eric J.
Schellhammer, Paul F.
Higano, Celestia S.
Redfern, Charles H.
Nemunaitis, John J.
Valone, Frank H.
Verjee, Suleman S.
Jones, Lori A.
Hershberg, Robert M.
机构
[1] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA
[2] Sharp Healthcare, San Diego, CA USA
[3] Eastern Virginia Med Sch, Norfolk, VA 23501 USA
[4] Univ Washington, Seattle, WA 98195 USA
[5] Dendreon Corp, Seattle, WA USA
[6] Mary Crowley Med Res Ctr, Dallas, TX USA
关键词
D O I
10.1200/JCO.2005.04.5252
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid. phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study. Patients and Methods A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 'ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells. Results Of the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P =.052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P =.01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P =.002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P <.001). Sipuleucel-T therapy was well tolerated. Conclusion While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.
引用
收藏
页码:3089 / 3094
页数:6
相关论文
共 15 条
[1]   Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: Recommendations from the prostate-specific antigen working group [J].
Bubley, GJ ;
Carducci, M ;
Dahut, W ;
Dawson, N ;
Daliani, D ;
Eisenberger, M ;
Figg, WD ;
Freidlin, B ;
Halabi, S ;
Hudes, G ;
Hussain, M ;
Kaplan, R ;
Myers, C ;
Oh, W ;
Petrylak, DP ;
Reed, E ;
Roth, B ;
Sartor, O ;
Scher, H ;
Simons, J ;
Sinibaldi, V ;
Small, EJ ;
Smith, MR ;
Trump, DL ;
Vollmer, R ;
Wilding, G .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (11) :3461-3467
[2]   Immunotherapy (APC8015, Provenge®) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer:: A phase 2 trial [J].
Burch, PA ;
Croghan, GA ;
Gastineau, DA ;
Jones, LA ;
Kaur, JS ;
Kylstra, JW ;
Richardson, RL ;
Valone, FH ;
Vuk-Pavlovic, S .
PROSTATE, 2004, 60 (03) :197-204
[3]  
Burch PA, 2000, CLIN CANCER RES, V6, P2175
[4]   Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer [J].
Halabi, S ;
Small, EJ ;
Kantoff, PW ;
Kattan, MW ;
Kaplan, EB ;
Dawson, NA ;
Levine, EG ;
Blumenstein, BA ;
Vogelzang, NJ .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (07) :1232-1237
[5]   Cancer statistics, 2005 [J].
Jemal, A ;
Murray, T ;
Ward, E ;
Samuels, A ;
Tiwari, RC ;
Ghafoor, A ;
Feuer, EJ ;
Thun, MJ .
CA-A CANCER JOURNAL FOR CLINICIANS, 2005, 55 (01) :10-30
[6]   NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].
KAPLAN, EL ;
MEIER, P .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481
[7]  
Laus R., 2001, CANC RES THER CONTRO, V11, P1
[8]   Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer [J].
Petrylak, DP ;
Tangen, CM ;
Hussain, MHA ;
Lara, PN,J ;
Jones, JA ;
Taplin, ME ;
Burch, PA ;
Berry, D ;
Moinpour, C ;
Kohli, M ;
Benson, MC ;
Small, EJ ;
Raghavan, D ;
Crawford, ED .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (15) :1513-1520
[9]   A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma [J].
Saad, F ;
Gleason, DM ;
Murray, R ;
Tchekmedyian, S ;
Venner, P ;
Lacombe, L ;
Chin, JL ;
Vinholes, JJ ;
Goas, JA ;
Chen, B .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2002, 94 (19) :1458-1468
[10]   Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration [J].
Smaletz, O ;
Scher, HI ;
Small, EJ ;
Verbel, DA ;
McMillan, A ;
Regan, K ;
Kelly, WK ;
Kattan, MW .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (19) :3972-3982