What is the recommended approach to using Pluvicto (lutetium-177 psma) in treating advanced prostate cancer?

From the Guidelines

Pluvicto (lutetium-177-PSMA) is recommended for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have already undergone androgen receptor pathway inhibitor therapy and taxane-based chemotherapy. The standard regimen consists of 7.4 GBq (200 mCi) administered intravenously every 6 weeks for up to 6 cycles, as indicated by the results of the VISION trial 1. Before starting treatment, patients should undergo PSMA PET imaging to confirm adequate PSMA expression in tumor lesions, ensuring the treatment targets the correct cells. Treatment requires coordination with nuclear medicine specialists and oncologists to minimize potential side effects. Patients need regular monitoring of complete blood counts, kidney function, and salivary gland function during therapy, as the treatment can cause bone marrow suppression, among other side effects 1. Common side effects include dry mouth, nausea, fatigue, and potential bone marrow suppression, highlighting the need for careful patient selection and monitoring 1. Hydration before and after treatment is important to minimize radiation exposure to the kidneys. Pluvicto works by delivering targeted radiation therapy directly to prostate cancer cells expressing PSMA (prostate-specific membrane antigen), which is overexpressed in most prostate cancer cells, allowing for precise targeting of tumor tissue while minimizing damage to surrounding healthy tissues. The use of Pluvicto is supported by guidelines from the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), which recommend its use in patients with mCRPC who have received prior androgen receptor pathway inhibition and taxane-based chemotherapy 1. Key considerations for the use of Pluvicto include:

• Patient selection based on PSMA expression
• Dosing and administration
• Monitoring for side effects
• Coordination with nuclear medicine specialists and oncologists. The median overall survival (OS) was improved in the Lu-177-PSMA-617 group compared with the control group (15.3 vs 11.3 months; HR, 0.62; 95% CI, 0.52–0.74; P,.001), as reported in the NCCN guidelines 1. Similarly, the median progression-free survival (PFS) was improved in the Lu-177-PSMA-617 group compared with the control group (8.7 vs 3.4 months; HR, 0.40; 99.2% CI, 0.29–0.57; P,.001) 1. The incidence of grade 3 adverse events was significantly higher in the Lu-177-PSMA-617 group compared with the control group, emphasizing the need for careful monitoring and management of side effects 1. In patients with mCRPC who have received a novel androgen receptor axis inhibitor and docetaxel, Pluvicto is a recommended treatment option, along with cabazitaxel, as indicated by the ESMO guidelines 1. Overall, Pluvicto is a valuable treatment option for patients with mCRPC, offering improved survival outcomes and targeted therapy.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Important Safety Instructions PLUVICTO is a radiopharmaceutical; handle with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5. 1)]. Use waterproof gloves and effective radiation shielding when handling PLUVICTO Radiopharmaceuticals, including PLUVICTO, should be used by or under the control of healthcare providers 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 authorized to license the use of radiopharmaceuticals. 2. 2 Patient Selection Select patients with previously treated mCRPC for treatment with PLUVICTO using LOCAMETZ or another approved PSMA-11 imaging agent based on PSMA expression in tumors. Additional selection criteria were used in the VISION study [see Clinical Studies (14)]. Refer to the prescribing information for the PSMA imaging agent. 2.3 Recommended Dosage The recommended PLUVICTO dosage is 7. 4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression, or unacceptable toxicity.

The recommended approach to using Pluvicto (lutetium-177 psma) in treating advanced prostate cancer is to:

• Select patients with previously treated mCRPC for treatment with Pluvicto using LOCAMETZ or another approved PSMA-11 imaging agent based on PSMA expression in tumors.
• Administer Pluvicto at a dosage of 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression, or unacceptable toxicity.
• Follow the recommended dosage modifications for adverse reactions, which may include temporary dose interruption, dose reduction, or permanent discontinuation of treatment with Pluvicto 2. Key points to consider when using Pluvicto include:
• Handling Pluvicto with appropriate safety measures to minimize radiation exposure.
• Using Pluvicto under the control of healthcare providers who are qualified by specific training and experience in the safe use and handling of radiopharmaceuticals.
• Monitoring patients for adverse reactions and adjusting the dosage accordingly.

From the Research

Recommended Approach to Using Pluvicto

The recommended approach to using Pluvicto (lutetium-177 psma) in treating advanced prostate cancer is as follows:

• The FDA approved Pluvicto 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 pathway inhibition and taxane-based chemotherapy 3, 4.
• The recommended dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity 3.
• Pluvicto has been shown to significantly prolong overall survival and imaging-based progression-free survival in patients with PSMA-positive mCRPC 3, 4.

Efficacy and Safety

The efficacy and safety of Pluvicto have been demonstrated in several clinical trials, including the VISION trial, which showed a statistically significant and clinically meaningful improvement in overall survival and imaging-based progression-free survival 3, 4.

• The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving Pluvicto were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation 3.
• The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving Pluvicto were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium 3.

Real-World Data Analysis

A real-world data analysis of efficacy and survival after lutetium-177 labelled PSMA ligand therapy in metastatic castration-resistant prostate cancer showed that:

• A ≥ 50% PSA decline was observed in 56% of patients, while any PSA decline occurred in 75% of men 5.
• Median values of overall survival, PSA progression-free survival, and PET/CT progression-free survival were 12,4, and 6 months, respectively 5.
• Predominantly lymph node metastatic disease and chemotherapy-naïve status were significant pre-therapy factors associated with longer survival 5.
• Baseline PSA was significantly linked to survival outcomes, with lower levels predicting a lower risk of death and disease progression 5.