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: Christopher R Heery, Ravi A Madan, Mark N Stein, Walter M Stadler, Robert S Di Paola, Myrna Rauckhorst, Seth M Steinberg, Jennifer L Marté, Clara C Chen, Italia Grenga, Renee N Donahue, Caroline Jochems, William L Dahut, Jeffrey Schlom, James L Gulley
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 42 Pg. 69014-69023 (10 18 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27486817 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Cancer Vaccines
• Organometallic Compounds
• Organophosphorus Compounds
• Radioisotopes
• Radiopharmaceuticals
• samarium Sm-153 lexidronam
• Prostate-Specific Antigen

Topics

• Aged
• Aged, 80 and over
• Beta Particles
• Bone Neoplasms (drug therapy, radiotherapy)
• Cancer Vaccines (therapeutic use)
• 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, radiotherapy)
• Radioisotopes (administration & dosage)
• Radiopharmaceuticals (administration & dosage)
• Treatment Outcome