Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Comparing between best medical cares versus best medical care + radioligand therapy with 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer. It was shown that radioligand therapy with 177Lu-PSMA-617 improves overall survival and radiographic progression-free survival when used as an adjunct to the routine treatment modalities in patients with castration-resistant metastatic prostate cancer. The study was published in The New England Journal of Medicine, June 2021, titled: Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer.

It is generally characterized by an increase in levels of Prostate-specific antigen (PSA), despite low levels of testosterone. Additionally, it also spreads to other parts of the body, like lymph nodes, bones, liver, and lungs. When prostate cancer reaches this stage, it fails to respond to the usual treatments thus increasing the mortality associated with it.

Prostate-specific membrane antigen (PSMA) is highly conveyed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)–PSMA-617 is a radioligand therapy (RLT) using beta-particle radiation to PSMA-expressing prostate cancer cells.

For the vision study, Sarto r O et. Al, conducted an international, open-label, phase 3 trial assessing 177Lu-PSMA-617 RLT in patients who had previously treated metastatic castration-resistant prostate cancer with at least one androgen-receptor–pathway inhibitor and one or two taxane chemotherapy regimens in 831 subjects who had PSMA-positive gallium-68 ( 68Ga)–labeled PSMA-11 PET-CT scans.

All participants were randomly divided into two groups in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) and routine standard care or standard care alone. The standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary endpoints were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively.

Key secondary endpoints were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before following treatment against cancer. The findings of the study are as follows: Lu-PSMA-617 and standard care significantly increased both imaging-based progression-free (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P<0.001). The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 as compared to just standard care (52.7% vs. 38.0%). However, quality of life was not adversely affected.

Reference:

1. Sartor O et Al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. The New England Journal of Medicine. 10.1056/NEJMoa210732.