[ 177 Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial.
177Lu-prostate-specific membrane antigen-617 with androgen deprivation therapy plus androgen receptor pathway inhibitor lowered risk of progression or death by 28%.
[ 177 Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial.
A contemporary standard of care for patients with metastatic androgen pathway modulator-naive/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is androgen deprivation therapy (androgen deprivation therapy) plus an androgen receptor pathway inhibitor (androgen receptor pathway inhibitor) until progression.
PSMAddition aimed to evaluate the efficacy and safety of [ 177 Lu]Lu-prostate-specific membrane antigen-617 ( 177 Lu-prostate-specific membrane antigen-617) combined with androgen deprivation therapy plus androgen receptor pathway inhibitor in prostate-specific membrane antigen (prostate-specific membrane antigen)-positive metastatic APMN/S prostate cancer.
Were randomly assigned 1:1 to open-label, intravenous 177 Lu-PSMA-617 (7·4 GBq [200 mCi] ±10% every 6 weeks for up to six cycles) with androgen deprivation therapy plus androgen receptor pathway inhibitor ( 177 Lu-PSMA-617 arm) or androgen deprivation therapy plus androgen receptor pathway inhibitor (control arm).
Grade 3 or worse adverse events occurred in 286 (51%) of 564 patients in the 177 Lu-PSMA-617 arm and 243 (43%) of 565 patients in the control arm.
Serious adverse events occurred in 180 (32%) of 564 patients in the 177 Lu-PSMA-617 arm and 162 (29%) of 565 in the control arm; of which 17 (3%) in the 177 Lu-PSMA-617 arm were 177 Lu-PSMA-617-related.
The most common adverse event was dry mouth, in 258 (46%) patients in the 177 Lu-PSMA-617 arm and 21 (4%) patients in the control arm; all were grade 1 or 2 and none were serious.
Other common adverse events with higher incidence in the 177 Lu-PSMA-617 arm included cytopenias and gastrointestinal disturbances.
Combining 177 Lu-prostate-specific membrane antigen-617 with androgen deprivation therapy plus androgen receptor pathway inhibitor prolonged radiographic progression-free survival in patients with prostate-specific membrane antigen-positive metastatic APMN/S prostate cancer.
Although adverse events were more frequent, there were no unexpected safety findings associated with the drug combination.
Therefore, combining 177 Lu-prostate-specific membrane antigen-617 with androgen deprivation therapy plus androgen receptor pathway inhibitor might be a new treatment option in metastatic APMN/S prostate cancer.