Pluvicto (Lutetium Therapy) Received FDA Approval for Advanced Prostate Cancer

Pluvicto (Lutetium Lu 177 vipivotide tetraxetan) was approved for adults previously treated with androgen receptor inhibition and taxane-based chemotherapy who have prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mKDPK) by the FDA (US Food and Drug Administration) on March 23, 2022.

On the same day, to determine eligibility for this PSMA-directed radioactive Lutetium therapy, the FDA also approved a radioactive diagnostic agent for use in positron emission tomography (PET), Locametz. Locametz is the first radioactive diagnostic agent approved for selecting patients for treatment with a radioligand therapeutic agent.

Mechanism of Action of Targeted Molecular Radionuclide Therapy

Lutetium Lu 177 vipivotide tetraxetan binds to prostate-specific membrane antigen (PSMA) on prostate cancer cells to both image and destroy tumor cells.

The radioactive peptides administered intravenously during treatment (Lutetium Lu 177 vipivotide tetraxetan) attach to the targeted cancer cells, emit large amounts of radiation and can destroy the cancerous cells. Patients may need to stay in hospital for a few days after treatment. Treatment generally requires 4-6 cycles.

FDA Approval Based on the VISION Study

PSMA positivity in the tumors of patients with previously treated mKDPK was detected using Locametz or another approved PSMA-11 imaging agent.

PSMA-positive mKDPK was defined as having at least one tumor with greater gallium (Ga 68) gozetotide uptake than normal liver.

The efficacy of Lutetium therapy was evaluated in a randomized, multicenter, open-label study (VISION) comparing Pluvicto plus best standard of care with best standard of care alone in men with progressive PSMA-positive mKDPK. All patients received a GnRH analog or had previously undergone bilateral orchiectomy (surgical castration, a procedure to remove both testes). Patients had to have received at least one previous androgen receptor inhibition treatment and 1 or 2 taxane-based chemotherapy regimens. They received Pluvicto 7.4 GBq plus best standard of care every 6 weeks for up to 6 doses, or best standard of care alone.

Results

Overall survival and radiographic progression-free survival initially showed statistically significant improvements.

• Median overall survival was 15.3 months in the Pluvicto group and 11.3 months in the other group.
• The hazard ratio for overall survival comparing Pluvicto plus best standard of care with best standard of care alone was 0.62. 

The most common side effects in patients receiving Pluvicto (≥20%) were:

• Fatigue
• Dry mouth
• Nausea
• Anemia
• Decreased appetite
• Constipation

The most common laboratory abnormalities in patients receiving Pluvicto (≥30%) were:

• Decreased lymphocytes
• Decreased hemoglobin
• Decreased leukocytes
• Decreased platelets
• Decreased calcium
• Decreased sodium

Treatment with pluvicto can also cause risks of radiation exposure, myelosuppression (reduced bone marrow activity) and renal toxicity. The safety follow-up period in the VISION study is insufficient to detect late radiation-related toxicities.

The recommended Pluvicto dose is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression or unacceptable toxicity.