6) and after evaluation of the patient by a qualified physician. Radiopharmaceuticals, including Pluvicto, should be used by or under the control of healthcare professionals who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals, and whose experience and training have been approved by the appropriate governmental agency authorised to license the use of radiopharmaceuticals.
4). Waterproof gloves and effective radiation shielding should be used when handling Pluvicto. Patient identification Patients should be identified for treatment by PSMA imaging. Posology The recommended Pluvicto dose is 7,400 MBq intravenously every 6 weeks (±1 week) for a total of 6 doses.
Treatment monitoring Laboratory tests should be performed before and during treatment with Pluvicto. • Haematology (haemoglobin, white blood cell count, absolute neutrophil count, platelet count) • Kidney function (serum creatinine, calculated creatinine clearance [CLcr]) • Liver function (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood serum albumin, total blood bilirubin) Dose modifications for adverse drug reactions (ADRs) Recommended dose modifications of Pluvicto for ADRs are provided in Table 1.
Management of severe or intolerable ADRs may require temporary dose interruption, dose reduction or permanent discontinuation of treatment with Pluvicto. If a treatment delay due to an adverse drug reaction persists for > 4 weeks, treatment with Pluvicto must be discontinued.
The dose of Pluvicto may be reduced by 20% to 5 900 MBq once; the dose should not be re-escalated. If a patient has further adverse drug reactions that would require an additional dose reduction, treatment with Pluvicto must be discontinued.
Table 1 Recommended dose modifications of Pluvicto for ADRs ADR Severitya Dose modification Dry mouth Grade ≥3 Reduce Pluvicto dose by 20% to 5 900 MBq. Gastrointestinal toxicity Grade ≥3 (not amenable to medical intervention) Withhold Pluvicto until improvement to grade 2 or baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq. Grade 2 Withhold Pluvicto until improvement to grade 1 or baseline. Manage as deemed appropriate. The use of growth factors is permitted but should be discontinued once improved to grade 1 or baseline.
Checking haematinic levels (iron, B12 and folate) and providing supplementation is advocated. Transfusions may be given as clinically indicated. Myelosuppresion (anaemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia) Grade ≥3 Withhold Pluvicto until improvement to Grade 1 or baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq. Renal toxicity Defined as: • Confirmed serum creatinine increase (grade ≥2) • Confirmed CLcr < 30 mL/min; calculate using Cockcroft-Gault with actual body weight Withhold Pluvicto until improvement.
Defined as: • Confirmed ≥40% increase from baseline serum creatinine and • Confirmed >40% decrease from baseline CLcr; calculate using Cockcroft-Gault with actual body weight Withhold Pluvicto until improvement or return to baseline.
Reduce Pluvicto dose by 20% to 5 900 MBq. Recurrent renal toxicity (grade ≥3) Permanently discontinue Pluvicto. Spinal cord compression Any Withhold Pluvicto until the compression has been adequately treated and any neurological sequela have stabilised and ECOG performance status has stabilised.
Fracture in weight-bearing bones Any Withhold Pluvicto until the fracture has been adequately stabilised/treated and ECOG performance status has stabilised. AST or ALT elevation AST or ALT >20 times ULN in the absence of liver metastases Permanently discontinue Pluvicto.
Abbreviations:
CLcr, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ULN, upper limit of normal. Grading according to most current Common Terminology Criteria for Adverse Events (CTCAE).
a The same thresholds are also applicable to baseline values at the time of treatment initiation with Pluvicto. 2). Renal impairment No dose adjustment is recommended for patients with mild (baseline CLcr 60 to 89 mL/min by Cockcroft-Gault) to moderate (CLcr 30 to 59 mL/min) renal impairment.
2). Hepatic impairment No dose adjustment is recommended for patients with hepatic impairment. Paediatric population There is no relevant use of Pluvicto in the paediatric population in the indication of treatment of PSMA-expressing prostate cancer.
Method of administration Pluvicto is for intravenous use. It is a ready to use radiopharmaceutical medicinal product for single use only. Preparation instructions • Aseptic technique and radiation shielding should be used when handling or administering Pluvicto, using tongs as needed to minimise radiation exposure.
• The product should be visually inspected under a shielded screen for particulate matter and discoloration prior to administration. The vial should be discarded if particulates or discoloration are present. • The Pluvicto solution should not be injected directly into any other intravenous solution.
• The amount of radioactivity delivered to the patient should be confirmed with an appropriately calibrated dose calibrator prior to and after each Pluvicto administration. Administration instructions The recommended dose of Pluvicto may be administered intravenously as an injection using the syringe method, as […]