Brand: Pluvicto

Initial US Approval

  • 2022 (VISION, March 23, 2022). Expanded March 28, 2025 (PSMAfore) and July 31, 2026 (PSMAddition).1,5,6,7

Indications

PSMA-Positive mAPMN/S Prostate Cancer:

  • In combination with ARPI therapy for adult patients with PSMA-positive metastatic androgen pathway modulation-naive or -sensitive (mAPMN/S) prostate cancer (previously termed metastatic hormone-sensitive prostate cancer).1

PSMA-Positive mAPMR Prostate Cancer:

  • Adult patients with PSMA-positive metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer who have been treated with ARPI therapy and are considered appropriate to delay taxane-based chemotherapy, or who have received prior taxane-based chemotherapy.1
  • Patient selection: PSMA expression by Locametz or another approved PSMA PET product; additional selection criteria were used in the trials.1

Recommended Dose/Route

  • 7.4 GBq (200 mCi) IV every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity. mAPMN/S: given with an ARPI (see the ARPI label for dosing). mAPMR: patients should also receive a GnRH analog or have had bilateral orchiectomy.1
  • Patients should stay well hydrated and void frequently, particularly after each dose.1

Dose Modification for Adverse Reactions

Figure

Pivotal Study

PSMAddition (NCT04720157)

  • Key Inclusion Criteria: PSMA-positive mAPMN/S disease with at least 1 metastatic lesion on conventional imaging; prior therapy limited to neoadjuvant/adjuvant ADT and up to 45 days of ADT and/or ARPI for metastatic disease.1,4
  • Treatment: randomized 1:1, open label, Pluvicto plus investigator's-choice ARPI (n=572) vs ARPI alone (n=572), each with ADT; 70% high-volume disease.1

PSMAfore (NCT04689828)

  • Key Inclusion Criteria / Treatment: taxane-naive mCRPC progressing on 1 prior ARPI; randomized 1:1 to Pluvicto (n=234) or change of ARPI (n=234).1,3

VISION (NCT03511664)

  • Key Inclusion Criteria / Treatment: mCRPC after at least 1 ARPI and 1 or 2 taxane regimens; randomized 2:1 to Pluvicto plus best standard of care (n=551) or best standard of care alone (n=280).1,2
Figure
  • Fair balance: in PSMAfore, OS was not significantly improved, with 60% of control patients crossing over to Pluvicto (crossover-adjusted HR, 0.59, exploratory). In PSMAddition, OS data are immature. VISION rPFS was statistically significant but its interpretation is limited by early control-arm dropout.1,3,8

Safety

PSMAddition (N=564)

  • Summary: serious adverse reactions 32%, fatal 2.7%, discontinuation 8%, dose reduction 3.9%, dose interruption 12%; median 6 doses.1
  • Key warnings: radiation exposure (limit close contact after each dose); myelosuppression (grade 3 or 4 decreased leukocytes 7%, neutrophils 4.4%, hemoglobin 4.3%); renal toxicity (grade 3 or 4 acute kidney injury 1.6%); embryo-fetal toxicity (contraception for 14 weeks after the last dose); infertility.1
Figure

VISION (N=529)

  • Summary: serious adverse reactions 37%, fatal 3%, discontinuation 12%, dose reduction 6%, dose interruption 16%. Most common: fatigue 48%, dry mouth 39%, nausea 36%; grade 3 or 4 decreased hemoglobin 15% and platelets 9%; grade 3 or higher pancytopenia 1.1%.1

References

  1. Pluvicto (lutetium Lu 177 vipivotide tetraxetan) injection. Prescribing information. Novartis Pharmaceuticals Corporation; revised 07/2026. Accessed October 2026.
  2. 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
  3. Morris MJ, Castellano D, Herrmann K, et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore). Lancet. 2024;404(10459):1227-1239. doi:10.1016/S0140-6736(24)01653-2
  4. Tagawa ST, Sartor O, Piulats JM, et al. [177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition). Lancet. 2026;408(10557):793-807. doi:10.1016/S0140-6736(26)01092-5
  5. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. US Food and Drug Administration. March 23, 2022.
  6. FDA expands Pluvicto's metastatic castration-resistant prostate cancer indication. US Food and Drug Administration. March 28, 2025.
  7. FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naive or -sensitive prostate cancer. US Food and Drug Administration. July 31, 2026.
  8. Fizazi K, Chi KN, Shore ND, et al. Final overall survival and safety analyses of the phase III PSMAfore trial. Ann Oncol. 2025;36(11):1319-1330. doi:10.1016/j.annonc.2025.07.003