Samarium-153-EDTMP (Quadramet®) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial

• Published in: Oncotarget 2016-10, Vol.7 (42), p.69014-69023
• Main Authors: Heery, Christopher R, Madan, Ravi A, Stein, Mark N, Stadler, Walter M, Di Paola, Robert S, Rauckhorst, Myrna, Steinberg, Seth M, Marté, Jennifer L, Chen, Clara C, Grenga, Italia, Donahue, Renee N, Jochems, Caroline, Dahut, William L, Schlom, Jeffrey, Gulley, James L
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Beta Particles; Bone Neoplasms - drug therapy; Bone Neoplasms - radiotherapy; Cancer Vaccines - therapeutic use; Clinical Research Paper; Disease Progression; Disease-Free Survival; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds - administration & dosage; Organophosphorus Compounds - administration & dosage; Osteoblasts - metabolism; Phenotype; Prostate-Specific Antigen - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Radioisotopes - administration & dosage; Radiopharmaceuticals - administration & dosage; Treatment Outcome
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.10883

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.