FDA Expands Pluvicto Indication in Prostate Cancer Subset

The U.S. Food and Drug Administration (FDA) has announced that it will expand the indication for Pluvicto (lutetium Lu 177 vipivotide tetraxetan) to include adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are appropriate for delaying taxane-based chemotherapy.

This expansion comes following the initial regulatory approval of the radioligand therapy in March 2022. At that time, the FDA approved the treatment for adult patients with PSMA-positive mCRPC who had previously undergone other anticancer therapies, including androgen receptor pathway inhibitors and taxane-based chemotherapy.

Adult patients with previously treated mCRPC should be selected for Pluvicto using Locametz (gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) product based on PSMA expression in tumors, according to the FDA’s announcement.

The Efficacy and Safety of the Agent

The efficacy of the agent evaluated in PSMAfore, a randomized, multicenter, open-label trial which evaluated 468 patients with PSMA-positive mCRPC who had progressed on one ARPI and were considered suitable for delaying taxane-based chemotherapy. Patients were randomly assigned to receive Pluvicto (7.4 gigabecquerels [GBq] [200 millicuries, mCi] every six weeks for six doses) or a change in ARPI. Patients who progressed on the ARPI arm were allowed to cross over to the experimental therapy.

Median radiographic progression-free survival was 9.3 months in the Pluvicto arm compared with 5.6 months in the ARPI arm. Comparatively, the median overall survival was 24.5 months and 23.1 months each arm, respectively. Sixty percent (141 patients) of patients randomized to the ARPI arm crossed over to receive Pluvicto following progression.

Side effects were consistent with prior experiences on Pluvicto, of which treatment may result in radiation exposure, myelosuppression and renal toxicity.

The recommended dose for Pluvicto is 7.4 GBq (200 mCi) intravenously, through the vein, every six weeks for six doses or until disease progression or unacceptable toxicity occurs.

The primary efficacy outcome was radiographic progression-free survival as assessed by blinded independent central review. Overall survival was also measured.

To participate in the clinical study, patients must be at least 18 years old and provide informed consent before enrolling. They should be in good physical condition, as indicated by an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as well as must have a confirmed diagnosis of prostate adenocarcinoma through laboratory tests.

Participants need to have a positive 68Ga-PSMA-11 PET/CT scan and have low testosterone levels. Furthermore, they should have previously been treated with one second-generation androgen receptor-directed therapy. The cancer must have continued to progress despite treatment, as shown by at least one of the following: increasing PSA levels over two separate tests at least one week apart, new or growing soft-tissue tumors or new bone lesions detected on imaging. Patients must also have at least one metastatic lesion visible on scan before randomization.

Before enrolling, patients should have recovered from prior treatments, such as chemotherapy or radiation, with only mild or moderate lingering side effects (except for hair loss). Participants also need to have healthy organ function, including adequate blood cell counts, liver function, kidney function and sufficient albumin levels.

Finally, patients must be eligible for a change in their treatment as determined by their doctor. Those who have previously experienced both disease progression and severe side effects specific treatments are not eligible for this study.

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