Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial
Autor: | Emmanuel S. Antonarakis, Adam S. Kibel, Evan Y. Yu, Lawrence I. Karsh, Aymen Elfiky, Neal D. Shore, Nicholas J. Vogelzang, John M. Corman, Frederick E. Millard, Johnathan C. Maher, Nancy N. Chang, Todd DeVries, Nadeem A. Sheikh, Charles G. Drake |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_specialty T-Lymphocytes medicine.medical_treatment Lymphocyte Activation Cancer Vaccines law.invention Metastasis Androgen deprivation therapy 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Clinical endpoint Humans Aged Aged 80 and over Tissue Extracts Prostatectomy business.industry ELISPOT Prostatic Neoplasms Cancer Androgen Antagonists Middle Aged Prostate-Specific Antigen medicine.disease Sipuleucel-T 030104 developmental biology Endocrinology 030220 oncology & carcinogenesis Androgens Immunotherapy Neoplasm Recurrence Local business medicine.drug |
Zdroj: | Clinical Cancer Research. 23:2451-2459 |
ISSN: | 1557-3265 1078-0432 |
Popis: | Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis. Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time. Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase–specific humoral responses increased significantly versus baseline (P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P = 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08–0.67; P = 0.007). Sipuleucel-T with ADT was generally well tolerated. Conclusions: Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation. Clin Cancer Res; 23(10); 2451–9. ©2016 AACR. |
Databáze: | OpenAIRE |
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