The FDA has approved lutetium-177 vipivotide tetraxetan (177Lu-PSMA-617) (Pluvicto™, Advanced Accelerator Applications, Novartis) for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have undergone treatment with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. In addition, the FDA approved gallium-68 gozetotide (68Ga-PSMA-11) (Locametz®, Novartis), a radioactive diagnostic agent for positron emission tomography (PET) of PSMA-positive lesions, to help in the selection process of patients with metastatic prostate cancer for whom 177Lu-PSMA-617 therapy is designated.
"Metastatic castration-resistant prostate cancer remains incurable and fatal, despite the availability of multiple classes of therapy that delay disease progression and prolong life," wrote Oliver Sartor, MD, Professor of Medicine at Tulane University School of Medicine, and colleagues, in their published results of VISION (NCT03511664), on which the approval was based. "Radioligand therapies such as 177Lu-PSMA-617 can target prostate cancer cells while sparing most normal tissues in patients who have been selected with the use of imaging to confirm radionuclide binding."
The phase 3, open-label, multicenter trial enrolled 831 male patients with PSMA-positive mCRPC determined using 68Ga-PSMA-11 PET–CT scanning who had received at least one AR pathway inhibitor and one or two prior taxane-based chemotherapy regimens. Eligible patients had at least one PSMA-positive metastatic lesion determined by 68Ga-PSMA-11 uptake greater than that of liver parenchyma using 68Ga-PSMA-11 PET–CT scanning and no PSMA-negative lesions. In addition, all patients received a gonadotropin-releasing hormone (GnRH) analog, unless they had a prior bilateral orchiectomy. Patients were randomized in a 2:1 ratio to receive 177Lu-PSMA-617 plus standard care (n=551) or standard care alone (n=280). Those receiving 177Lu-PSMA-617 were administered 7.4 GBq (200 mCi) via intravenous (IV) infusion every six weeks for four cycles, with the treating physician eligible to add two additional cycles if preferred, for a maximum of six cycles. The coprimary end points were radiographic progression-free survival and overall survival. Key secondary end points included time to first symptomatic skeletal event, overall response rate, and disease control rate.
At a median follow-up of 20.9 months, data revealed that 177Lu-PSMA-617 in addition to standard care significantly prolonged median radiographic progression-free survival compared with standard care alone (8.7 vs 3.4 months). Median overall survival was also significantly prolonged in patients who received 177Lu-PSMA-617 compared with standard care alone (15.3 vs 11.3 months). Patients treated with 177Lu-PSMA-617 and standard care experienced a notable improvement in the secondary end point of median time to first symptomatic skeletal event or death (11.5 vs 6.8 months). All other secondary end points were reported in favor towards 177Lu-PSMA-617.
Adverse reactions in ≥20% of patients receiving 177Lu-PSMA-617 included fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. Laboratory abnormalities in ≥30% of patients receiving 177Lu-PSMA-617 included decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. Caution is also noted for risk of radiation exposure, myelosuppression, and renal toxicity for patients being treated with 177Lu-PSMA-617.
"In this trial, the addition of 177Lu-PSMA-617 to standard care significantly extended survival among patients with metastatic castration-resistant prostate cancer and progressive disease who had received previous treatment with one or more androgen receptor pathway inhibitors and one or two taxanes," concluded Dr. Sartor and colleagues in their publication in the New England Journal of Medicine. "Treatment with 177Lu-PSMA-617 was associated with toxic effects that were mainly of grade 3 or lower, and this therapy also extended the time to symptomatic skeletal events, prolonged the time to worsening of health-related quality of life and pain, and delayed biochemical progression."
The recommended dose of 177Lu-PSMA-617 is 7.4 GBq (200 mCi) via IV every six weeks for up to six doses or until disease progression or unacceptable toxicity.
For More Information
US Food and Drug Administration (2022). FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-
Image Credit: Yale Rosen. Licensed under CC BY-SA 2.0