PLUVICTO

What it is

PLUVICTO is a solution for injection containing lutetium (177Lu) vipivotide tetraxetan, with 1,000 MBq per mL at the date and time of calibration. It is a clear, colourless to slightly yellow solution with a pH range of 4.5 to 7.0. The active moiety is the radionuclide lutetium-177 linked to a targeting moiety that binds to PSMA, a transmembrane protein highly expressed in prostate cancer. Upon binding to PSMA-expressing cancer cells, the beta-minus emission from lutetium-177 delivers therapeutic radiation to the targeted cell and surrounding cells, inducing DNA damage which can lead to cell death.

Approved indications

— Treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

Dosing overview

The recommended PLUVICTO dose is 7,400 MBq administered intravenously every 6 weeks (± 1 week) for up to a total of 6 doses or until disease progression or unacceptable toxicity. Patients should be identified for treatment by PSMA imaging. Medical castration with a gonadotropin-releasing hormone (GnRH) analogue should be continued during treatment in patients not surgically castrated. The dose may be reduced by 20% once (to a dose of 5,900 MBq); the dose should not be re-escalated.

Key safety warnings

PLUVICTO can cause severe and life-threatening myelosuppression, including anaemia, thrombocytopaenia, leukopaenia, and neutropaenia. Two deaths due to intracranial haemorrhage and subdural haematoma in association with thrombocytopaenia were observed, and one death due to sepsis and concurrent neutropaenia was observed in patients who received PLUVICTO. Haematology laboratory tests, including haemoglobin, white blood cell count, absolute neutrophil count, and platelet count, should be performed before and during treatment. Renal toxicity occurred more frequently in patients who received PLUVICTO plus best standard of care compared to patients who received best standard of care alone. Patients should be advised to remain well hydrated and to urinate frequently before and after administration. Kidney function laboratory tests, including serum creatinine and calculated creatinine clearance, should be performed before and during treatment. PLUVICTO contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Radiation exposure to patients, medical personnel, and others should be minimised during and after treatment consistent with institutional good radiation safety practices. This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Radiations of lutetium (177Lu) vipivotide tetraxetan may potentially have toxic effects on male gonads and spermatogenesis. The recommended cumulative dose of 44,400 MBq results in a radiation absorbed dose to the testes within the range where PLUVICTO may cause infertility.

Contraindications

PLUVICTO is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

Regulatory history

PLUVICTO was first listed on the Australian Register of Therapeutic Goods on 17 July 2024. PLUVICTO was approved by the TGA on 16 July 2024 for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy, following a collaborative review under Project Orbis.