Pluvicto®▼ (lutetium [177Lu] vipivotide tetraxetan) is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes.1
Locametz®▼(gozetotide) is for diagnostic use only. Locametz, after radiolabelling with gallium-68, is a radioactive diagnostic agent indicated for the identification of prostate-specific membrane antigen (PSMA)-positive lesions by positron emission tomography (PET) in adult patients with prostate cancer.2
Clinical Trials
VISION was an international, prospective, randomised, open-label, multicentre, Phase III study (N=831) to assess the efficacy and safety profile of Pluvicto plus investigator-chosen best standard of care (BSoC) in the investigational arm, versus BSoC in the control arm. Patients with PSMA positron emission tomography (PET)-scan positive mCRPC, and progression after prior taxane and androgen receptor pathway inhibitors, were randomised in a 2:1 ratio in favour of the investigational arm. The alternate primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS).3
View the study design for VISION below.
*Documented progressive mCRPC was based on at least one of three criteria: serum PSA progression, soft-tissue progression or bone disease progression.5 Soft tissue progression was defined as an increase ≥20% in the sum of the diameter of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. Progression of bone disease was defined as evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria). Serum PSA progression was defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior, minimal start value is 2.0 ng/mL.5
†PSMA-positive disease sites were defined as ≥1 PSMA-positive lesions anywhere in the body, with PSMA PET imaging ligand uptake greater than that of liver parenchyma in one or more metastatic lesions in any organ system. No size criteria were applied on PSMA-positive lesions.3
§Imaging-based progression-free survival was defined as the time from randomisation to independently centrally-reviewed disease progression (defined according to the PCGW3 criteria) or death.3
¶First SSE defined as first new symptomatic pathological bone fracture, spinal cord compression, tumour-related orthopaedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death from any cause, whichever occurred first.5
‖Additional secondary endpoints included: safety and tolerability; HRQoL: EQ-5D-5L, FACT-P and BPI-SF; health economics; composite PFS (radiological, clinical or PSA progression); biochemical response: PSA, ALP and LDH levels.
Pluvicto + BSoC significantly extends survival in PSMA-positive mCRPC patients vs BSoC alone3
View the efficacy outcomes for VISION below.
Primary endpoints:
Secondary endpoints:
The most common ADRs (≥20%) occurring at a higher incidence in patients who received Pluvicto plus BSoC compared to BSoC alone include: fatigue (43.1%), dry mouth (39.3%), nausea (35.3%), anaemia (31.8%), decreased appetite (21.2%) and constipation (20.2%). The most common grade 3 to 4 ADRs (≥5%) occurring at a higher incidence in patients who received Pluvicto plus BSoC compared to BSoC alone include: anaemia (12.9%), thrombocytopenia (7.9%), lymphopenia (7.8%) and fatigue (5.9%).1
This list is not exhaustive; for further safety information please refer to the UK Summary of Product Characteristics.1
ADR, adverse drug reaction; ALP, alkaline phosphatase; AR, androgen receptor; ARPI, androgen receptor pathway inhibitor; BM, bone marrow; BPI-SF, brief pain inventory (short form); BSoC, best standard of care; CI, confidence interval; CNS, central nervous system; CT, computed tomography; DCR, disease control rate; ECOG-PS, Easter Cooperative Oncology Group performance status; EQ-5D-5L, 5-level EuroQol-5 dimension version; FACT-P, functional assessment of cancer therapy-prostate; HR, hazard ratio; HRQoL, health-related quality of life; LDH, lactic acid dehydrogenase; LHRH, luteinising hormone releasing hormone; mCRPC, metastatic castration-resistant prostate cancer; MRI, magnetic resonance imaging; ORR, objective response rate; OS, overall survival; PCWG3, Prostate Cancer Clinical Trials Working Group 3; PET, positron emission tomography; PSA, prostrate-specific antigen; PSMA, prostate-specific membrane antigen; R, randomisation; RLT, radioligand therapy; rPFS, radiographic progression-free survival; SSE, symptomatic skeletal event.
References:
- Pluvicto® (lutetium [177Lu] vipivotide tetraxetan) Summary of Product Characteristics..
- Locametz® (gozetotide) Summary of Product Characteristics.
- Sartor O, et al. N Engl J Med 2021;385(12):1091–1103.
- Sartor O, et al. N Engl J Med 2021 Sep;385(12):1091–1103. Supplementary appendix.
- Sartor O, et al. N Engl J Med 2021 Sep;385(12):1091–1103. Study protocol.
- Fizazi K, et al. Ann Oncol 2021 Sep;32 (Supplement 5):S626–S677.