Clinical Research Papers:
Samarium-153-EDTMP (Quadramet®) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial
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Christopher R. Heery1, Ravi A. Madan2, Mark N. Stein3, Walter M. Stadler4, Robert S. Di Paola3,7, Myrna Rauckhorst2, Seth M. Steinberg5, Jennifer L. Marté2, Clara C. Chen6, Italia Grenga1, Renee N. Donahue1, Caroline Jochems1, William L. Dahut2, Jeffrey Schlom1, James L. Gulley2
1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
2Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
3Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
4University of Chicago Medicine, Chicago, IL, USA
5Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
6National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
7Current affiliation: University of Kentucky College of Medicine Lexington, KY, USA
James L. Gulley, email: Gulleyj@mail.nih.gov
Keywords: therapeutic vaccine, radionuclide, prostate cancer, Quadramet®, cancer immunotherapy
Received: April 19, 2016 Accepted: June 26, 2016 Published: July 28, 2016
PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline > 30% compared with four patients (of 21) in the combination arm, including three with PSA decline > 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM.
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