In the VISION phase 3 trial in advanced PSMA-positive metastatic castration-resistant prostate cancer, adding lutetium-177-PSMA-617 to standard care prolonged imaging-based progression-free survival and overall survival.
Built / tested: 177Lu-PSMA-617
As reported in: Sartor, de Bono, Chi et al. (2021). Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine. doi:10.1056/nejmoa2107322
Bäck and colleagues attached astatine-211 to an anti-PSCA minibody; in mice it cut subcutaneous prostate tumour volumes by about 85% at six weeks and clearly inhibited growth of tumours in bone.
As reported in: Bäck, Jennbacken, Hagberg Thulin et al. (2020). Targeted alpha therapy with astatine-211-labeled anti-PSCA A11 minibody shows antitumor efficacy in prostate cancer xenografts and bone microtumors. EJNMMI Research. doi:10.1186/s13550-020-0600-z
Hammer and colleagues developed PSMA-TTC, a fully human PSMA antibody carrying the alpha emitter thorium-227, which showed strong antitumour activity in mouse models of prostate cancer, including models resistant to enzalutamide.
Built / tested: PSMA-TTC (BAY 2315497)
As reported in: Hammer, Hagemann, Zitzmann-Kolbe et al. (2020). Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer. Clinical Cancer Research. doi:10.1158/1078-0432.ccr-19-2268
In the Act.In.Sarc phase 2–3 trial in locally advanced soft-tissue sarcoma, hafnium oxide nanoparticles (NBTXR3) injected into the tumour before radiotherapy doubled the pathological complete response rate, 16% versus 8% with radiotherapy alone.
Publisher update notice: erratum
Built / tested: NBTXR3
As reported in: Bonvalot, Rutkowski, Thariat et al. (2019). NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2–3, randomised, controlled trial. The Lancet Oncology. doi:10.1016/s1470-2045(19)30326-2
Reinders and colleagues reviewed holmium-166 microspheres, a third type of microsphere for radioembolization of liver tumours in Europe; early studies showed a mean whole-liver dose of 60 Gy was safe and induced tumour response.
As reported in: Reinders, Smits, van Roekel et al. (2019). Holmium-166 Microsphere Radioembolization of Hepatic Malignancies. Seminars in Nuclear Medicine. doi:10.1053/j.semnuclmed.2019.01.008
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Müller and colleagues labelled PSMA-617 with terbium-161, which also emits conversion and Auger electrons; it distributed like lutetium-177-PSMA-617 in mice but reduced prostate cancer cell viability more, and extended survival of treated mice.
As reported in: Müller, Umbricht, Gracheva et al. (2019). Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging. doi:10.1007/s00259-019-04345-0
In the NETTER-1 phase 3 trial in 229 patients with advanced midgut neuroendocrine tumours, estimated 20-month progression-free survival was 65.2% with lutetium-177-Dotatate versus 10.8% with octreotide LAR alone.
Built / tested: 177Lu-Dotatate
As reported in: Strosberg, El-Haddad, Wolin et al. (2017). Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors. New England Journal of Medicine. doi:10.1056/nejmoa1607427
Kratochwil and colleagues reported two men with advanced prostate cancer whose PSA fell below measurable levels and whose scans showed complete response after experimental actinium-225-PSMA-617 alpha therapy; dry mouth was the only notable clinical side effect.
As reported in: Kratochwil, Bruchertseifer, Giesel et al. (2016). 225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. Journal of Nuclear Medicine. doi:10.2967/jnumed.116.178673
In a phase 3 trial in 921 men with castration-resistant prostate cancer and bone metastases, the alpha emitter radium-223 improved median overall survival to 14.9 months versus 11.3 months with placebo.
Built / tested: radium-223 dichloride
As reported in: Parker, Nilsson, Heinrich et al. (2013). Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer. New England Journal of Medicine. doi:10.1056/nejmoa1213755
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Salem and colleagues reported long-term outcomes for 291 patients with hepatocellular carcinoma treated with yttrium-90 microspheres delivered through the liver arteries; patients with Child-Pugh A disease benefited most.
As reported in: Salem, Lewandowski, Mulcahy et al. (2010). Radioembolization for Hepatocellular Carcinoma Using Yttrium-90 Microspheres: A Comprehensive Report of Long-term Outcomes. Gastroenterology. doi:10.1053/j.gastro.2009.09.006
In a phase 3 trial in 143 patients with relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin's lymphoma, yttrium-90 ibritumomab tiuxetan gave an 80% overall response rate versus 56% for rituximab.
Built / tested: 90Y ibritumomab tiuxetan
As reported in: Witzig, Gordon, Cabanillas et al. (2002). Randomized Controlled Trial of Yttrium-90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin’s Lymphoma. Journal of Clinical Oncology. doi:10.1200/jco.2002.11.076
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Palmedo and colleagues gave escalating doses of rhenium-188 HEDP to 22 prostate cancer patients with painful bone metastases; 64% reported pain relief, and low platelet and white-cell counts were the main side effects.
As reported in: Palmedo, Guhlke, Bender et al. (2000). Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. European Journal of Nuclear Medicine and Molecular Imaging. doi:10.1007/s002590050017
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In a double-blind placebo-controlled trial in 118 patients with painful bone metastases, a single 1.0 mCi/kg dose of samarium-153 lexidronam relieved pain within a week, lasting to at least week 16 in most patients who responded.
As reported in: Serafini, Houston, Resche et al. (1998). Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.. Journal of Clinical Oncology. doi:10.1200/jco.1998.16.4.1574
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