On July 31, the U.S. Food and Drug Administration (FDA) approved lutetium-177–labeled PSMA-617 (vipivotide tetraxetan, also known as LuPSMA-617; Pluvicto), a targeted radionuclide therapy, in combination with androgen receptor pathway inhibitor (ARPI) therapy for adults with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation–naive or–sensitive (mAPMN/S) prostate cancer (previously referred to as metastatic hormone-sensitive prostate cancer).
Patients with mAPMN/S prostate cancer should be selected for LuPSMA-617 using gallium Ga-68 gozetotide (Locametz), a radioactive diagnostic agent for positron-emission tomography (PET) of PSMA-positive lesions, or another approved PSMA PET product based on PSMA expression in tumors.
PSMAddition
Efficacy was evaluated in PSMAddition (ClinicalTrials.gov identifier NCT04720157), a randomized, multicenter, open-label trial in patients with PSMA-positive mAPMN/S prostate cancer. Patients were randomly assigned 1:1 to receive either LuPSMA-617 (7.4 GBq [200 mCi] every 6 weeks for six doses) in combination with an ARPI (n = 572) or an ARPI alone (n = 572). The administered ARPIs, per investigator’s choice, included abiraterone, apalutamide, enzalutamide, darolutamide, or another ARPI. Treatment with an ARPI in both arms could be continued until progressive disease or unacceptable toxicity. Patients received a gonadotropin-releasing hormone agonist or antagonist concurrently or had a bilateral orchiectomy.
The major efficacy outcome measure was radiographic progression–free survival (rPFS) as determined by blinded independent central review per Prostate Cancer Working Group 3-modified Response Evaluation Criteria in Solid Tumors version 1.1 criteria; overall survival was an additional efficacy outcome measure. The trial demonstrated a statistically significant improvement in rPFS in patients treated with LuPSMA-617 and an ARPI compared to an ARPI alone. Median rPFS was not reached in either arm (hazard ratio = 0.72, 95% confidence interval = 0.58–0.90, P = .002). The overall survival data were immature at the current analysis.
Adverse reactions were consistent with prior experience with LuPSMA-617. The prescribing information includes warnings and precautions for the risk of radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility.
Recommended Dosage
The recommended LuPSMA-617 dose in combination with ARPI is 7.4 GBq (200 mCi) every 6 weeks for six doses, or until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for the concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.
