FDA Approves Pluvicto for Progressive, PSMA-Positive Metastatic CRPC


The FDA has approved lutetium Lu 177 vipivotide tetraxetan for the treatment of adult patients with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer who have previously received other anticancer therapies.



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

The regulatory agency has also greenlit Locametz®, which is a radioactive diagnostic agent for PET of PSMA-positive lesions, including selection of patients with metastatic disease for whom the therapy is indicated. Notably, this is the first radioactive diagnostic agent that has received regulatory approval for patient selection in the use of a radioligand therapeutic agent.

The decision is supported by data from the phase 3 VISION trial (NCT03511664), which showed that when the targeted radioligand therapy was combined with standard of care (SOC), it resulted in a 38% reduction in the risk of death vs SOC alone in patients with PSMA-positive mCRPC patients who previously received AR pathway inhibition and taxane-based chemotherapy. The median overall survival (OS) in the investigative arm was 15.3 months vs 11.3 months in the control arm (HR, 0.62; 95% CI, 0.52-0.74; P < .001).

The radioligand therapy also significant reduced the risk of radiographic disease progression or death vs SOC alone. However, interpretation of the magnitude of the radiographic progression-free survival (PFS) effect was limited due to a high degree of censoring from early drop out in the control arm.

Moreover, approximately one-third of patients with evaluable disease at baseline expereinced an overall response per RECIST v1.1 criteria to lutetium Lu 177 vipivotide tetraxetan plus SOC vs 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,” Oliver Sartor, MD, Medical Director at Tulane Cancer Center, stated in a press release. “Pluvicto is a step forward in the evolution of precision medicine for prostate cancer.”

VISION enrolled patients with CRPC who had at least 1 metastatic lesion on baseline computed tomography, magnetic resonance imagine, or bone-scan imaging.3 Patients must have progressed following prior 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.

Moreover, patients needed to have an ECOG performance status ranging from 0 to 2, a life expectancy of at least 6 months, and acceptable organ and bone marrow function.

Study participants 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 given in those with evidence of response, per investigator discretion. Notably, SOC treatments could not comprise cytotoxic chemotherapy, systemic radioisotopes, immunotherapy, or agents considered to be investigational when the trial was designed.

Participants continued to receive standard treatment, with or without the 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 progression-free survival (PFS) and OS. Key secondary end points included objective response rate and disease control rate, as well as the time to first symptomatic skeletal event. Other end points included safety, health-related quality of life, pain, and biomarker outcomes such as PSA response.

Of a total of 1003 patients who underwent scanning, 831 patients were determined to meet the eligibility criteria for the trial and thus were randomized to received the radioligand therapy plus SOC (n = 551) or SOC alone (n = 280).

Baseline demographic and disease characteristics were found to be well balanced between the treatment arms and the randomization period.

Data published in the New England Journal of Medicine showed that at a median follow-up of 20.9 months, the median imaging-based PFS in the investigative arm was 8.7 months vs 3.4 months in the control arm (HR, 0.40; 95% CI, 0.29-0.57; P < .001).

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

Of the 248 patients with measurable target lesions per RECIST v1.1 criteria, 9.2% of patients in the investigative arm (n = 184) achieved a complete response vs 0% of those in the control arm (n = 64). Partial responses were reported in 41.8% and 3.0% of those on the investigative and control arms, respectively.

Notably, more patients on the radioligand therapy arm had confirmed reductions in the PSA level of at least 50% and 80% from baseline vs those on the SOC-alone arm. Regarding QOL, the time to deterioration in the FACT-P total score and BPI-SF pain intensity score also favored the radioligand therapy/SOC combination over SOC alone.

Patients were exposed to the radioligand therapy for a median of 6.9 months (range, 0.3-10.2), and patients 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).

Regarding safety, the most common any-grade adverse effects in the investigative arm included 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 who received the radionuclide therapy included decreased lymphocytes, hemoglobin, leukocytes, platelets, calcium, and sodium.

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


  1. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA; March 23, 2022. Accessed March 23, 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
  3. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi: 10.1056/NEJMoa2107322
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