FDA Approves Pluvicto for PSMA–Positive Metastatic Castration-Resistant Prostate Cancer


Pluvicto is indicated for the treatment of adults with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer who were previously administered other anticancer therapies.

The FDA has approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617) for the treatment of adults with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who were previously administered other anticancer therapies, such as androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.1,2

The FDA also granted approval to Locametz, a kit for the preparation of gallium Ga 68 gozetotide injection, as a radioactive diagnostic agent for PET of PSMA-positive lesions, including the selection of patients with metastatic disease for whom the therapy is indicated. This is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent, according to the manufacturer.

The approval was based on data from the phase 3 VISION trial (NCT03511664), which found combining the targeted radioligand therapy with standard of care (SOC) produced a 38% reduction in the risk of death compared with SOC alone in patients with PSMA-positive mCRPC previously administered AR pathway inhibition and taxane-based chemotherapy. The median overall survival (OS) in the investigative cohort was 15.3 months compared with 11.3 months in the control group (HR, 0.62; 95% CI, 0.52-0.74; < .001).

The treatment also lowered the risk of radiographic disease progression or death compared with SOC alone. Interpretation of the effect of the radiographic progression-free survival (PFS) response was limited because of a high degree of censoring from early drop out in the control arm, according to the investigators.

Further, approximately one-third of patients with evaluable disease at baseline had an overall response per RECIST v1.1 criteria to lutetium Lu 177 vipivotide tetraxetan plus SOC compared with 2% in the SOC-alone arm.

“The approval of Pluvicto is an important clinical advancement for people with progressing mCRPC, as it can significantly improve survival rates for those who have limited treatment options,” said Oliver Sartor, MD, medical director at Tulane Cancer Center, in a press release. “Pluvicto is a step forward in the evolution of precision medicine for prostate cancer.”

The study enrolled patients with CRPC with at least 1 metastatic lesion on baseline computed tomography, magnetic resonance imaging, or bone-scan imaging. Patients had to have progressed after previous treatment with 1 or more approved AR pathway inhibitor and with 1 or 2 taxane regimens. Patients also needed to have at least 1 PSMA-positive metastatic lesion.

The patients were randomized 2:1 to receive the radioligand therapy at a dose of 7.4 GBq (200 mCi) once every 6 weeks for 4 cycles plus SOC (n = 551) or SOC alone (n = 280). Two additional cycles of the radioligand therapy could be administered in patients with evidence of response, per investigator discretion, SOC treatments could not include cytotoxic chemotherapy, systemic radioisotopes, immunotherapy, or agents considered to be investigational when the trial was designed.

Participants received standard treatment, with or without radioligand therapy, until disease progression, intolerable toxicity, lack of clinical benefit, or a prohibited treatment was determined to be necessary.

The alternate primary end points of the trial were imaging-based PFS and OS. Secondary end points included objective response rate, disease control rate, and time to first symptomatic skeletal event.

Of patients who underwent scanning, 831 met the eligibility criteria for the trial and were randomized to receive the radioligand therapy plus SOC (n = 551) or SOC alone (n = 280).

A median follow-up of 20.9 months, the median imaging-based PFS in the investigative arm was 8.7 months compared with 3.4 months in the control arm (HR, 0.40; 95% CI, 0.29-0.57; < .001), according to data published in the New England Journal of Medicine.

Among 581 patients in the analysis set, the median time to first symptomatic skeletal event or death was 11.5 months in patients administered the radioligand therapy compared with 6.8 months in those who did not (HR, 0.50; 95% CI, 0.40-0.62; < .001).

Of 248 patients with measurable target lesions per RECIST v1.1 criteria, 9.2% in the investigative cohort (n = 184) achieved a complete response compared with 0% of patients in the control group (n = 64). Partial responses were found in 41.8% in the investigative cohort compared with 3.0% in the control group.

More patients in the investigative cohort had confirmed reductions in the PSA level of at least 50% and 80% from baseline compared with patients in the SOC arm. Patients were exposed to the radioligand therapy for a median of 6.9 months (range, 0.3-10.2), and started a median of 5 cycles (range, 1-6) of treatment and with a median cumulative dose of 37.5 GBq (range, 0.3-31.3).

The most common any-grade adverse effects in the investigative cohort were fatigue (43%), dry mouth (39%), nausea (35%), anemia (low red blood cell counts) (32%), decreased appetite (21%), and constipation (20%).

The most frequently experienced laboratory abnormalities that worsened from baseline in 30% or more of patients administered the radionuclide therapy included decreased lymphocytes, hemoglobin, leukocytes, platelets, calcium, and sodium.

Treatment with the newly-approved therapy may result in risk of radiation exposure, myelosuppression, and renal toxicity, according to the FDA.


  1. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA; March 23, 2022. Accessed March 24, 2022. https://bit.ly/3LaWA8w
  2. Novartis PluvictoTM approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis Pharma AG; March 23, 2022. Accessed March 23, 2022. https://bit.ly/3ivS3By
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