177Lu-PSMA-617 approved for use in patients with PSMA+ mCRPC

As of the 23rd March 2022, the U.S. Food and Drug Administration (FDA) has approved 177Lu-PSMA-617 (a.k.a. Lu 177 Vipivotide Tetraxetan) as a radioligand therapy for previously-treated patients with prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC).1 Patients must have previously undergone androgen receptor inhibition and 1-2 lines of taxane-based chemotherapy to be eligible.

Patients with mCRPC are in great need of effective treatments, as there are no curative therapies available and current standard life-prolonging therapies (in the U.S., these are commonly abiraterone/prednisone or enzalutamide) achieve an overall survival of approximately 2 years.2 There is a great unmet need for a treatment that can increase overall survival and maintain good quality of life in these patients.

PSMA is highly expressed on prostate cancer cells and metastatic lesions, and this high expression is a biomarker for poor survival in these patients. 177Lu-PSMA-617 is a beta-emitter which selectively targets PSMA+ cells and the tumor microenvironment.3

Lu 177 vipivotide tetraxetan’s approval in mCRPC is based on results from the Phase III randomized VISION trial (NCT03511664) which investigated the use of 177Lu-PSMA-617 in combination with standard of care.4 Prospective patients underwent PSMA PET scans to determine PSMA expression, and those who were determined to be PSMA+ (n = 831) were enrolled.3 Patients were randomized 2:1 to receive 177Lu-PSMA-617 plus best standard of care (BSOC) or BSOC alone. The primary endpoints of the study were radiographic progression-free survival (rPFS) and overall survival (OS), with secondary endpoints including occurrence of treatment-related adverse events, overall response rate, and duration of response.4

After a median follow-up of 20.9 months, patients in the experimental arm met both primary endpoints. The median rPFS was 8.7 months in the experimental arm compared to 3.4 in the control and the median OS was 15.3 months in the experimental arm compared to 11.3 months in the control.1,3 It is important to note that the FDA stated that analysis of rPFS was “limited due to a high degree of censoring from early drop out in the control arm”.1

A key limitation of 177Lu-PSMA-617 compared to BSOC is that 52.7% of patients in the experimental arm experienced grade 3 or higher adverse events, compared to 38% in the control arm. However, quality of life (a secondary endpoint) was not significantly impacted by this difference.3,4

We spoke to Prof. Scott Tagawa of Weill Cornell Medical College and New York Presbyterian Hospital, NY, at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, about the VISION trial.

This approval opens up another greatly needed avenue of treatment for these patients and could help them to achieve better survival outcomes, in combination with current BSOC.


  1. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. U.S. Food and Drug Administration. 2022 [cited 28th March 2022]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer
  2. George DJ, Sartor O, Miller K, et al. Treatment patterns and outcomes in patients with metastatic castration-resistant prostate cancer in a real-world clinical practice setting in the United States. Clinical genitourinary cancer. 2020 Aug 1.
  3. Sartor O, De Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. New England Journal of Medicine. 2021 Sep.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 30 April 2018 – 7 March 2022. Identifier: NCT03511664, Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION). Available from: https://clinicaltrials.gov/ct2/show/NCT03511664

Written by Helena Gibbon

Edited by Sol Yohannes