title: Samarium-153-EDTMP (Quadramet®) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial.
abstract: 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.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Heery
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Stein
authors.affiliation: University of Chicago Medicine, Chicago, IL, USA.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|Current affiliation: University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Di Paola
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Myrna
authors.initials: M
authors.lastname: Rauckhorst
authors.affiliation: Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marté
authors.affiliation: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Italia
authors.initials: I
authors.lastname: Grenga
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Donahue
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.affiliation: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001610:Beta Particles; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000008:administration & dosage*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010006:Osteoblasts / Q000378:metabolism; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000532:radiotherapy; D011868:Radioisotopes / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam; D017430:Prostate-Specific Antigen
keywords: cancer immunotherapy; prostate cancer; radionuclide; therapeutic vaccine; Quadramet®