Patients with metastatic castration-resistant prostate cancer (mCRPC) experienced improved prostate-specific antigen (PSA) progression-free survival (PSA-PFS) when treated with Pluvicto (Lu-PSMA-617) and Xtandi (enzalutamide) compared with Xtandi alone, according to interim findings from the phase 2 ENZA-p study presented at the 2023 European Society of Medical Oncology (ESMO) Congress in Madrid, Spain.
PSA-PFS has been defined in the Journal of Clinical Oncology as the time to two consecutive increases in PSA (a protein that is associated with the presence of prostate cancer in the body) of 50% and five or more nanograms/milliliter above nadir or death.
“This is the first randomized trial combining an androgen receptor signaling inhibitor, (Xtandi), with (Pluvicto). It provides strong evidence for an enhanced anti-cancer effect with the combination of (Xtandi) and (Pluvicto) based on the primary end point, PSA-PFS,” said Dr. Louise Emmett during an oral presentation of the findings at the ESMO meeting. Emmett is the director of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia.
Data from the study showed a median PSA-PFS of 13 months with the combination therapy compared with 7.8 months with Xtandi alone. Median radiographic PFS was 16 months with the combination therapy compared with 12 months for Xtandi alone.
Further, PSA 50% (decrease of at least 50% from baseline) response rates were 93% (77 of 83 patients) in the combination arm, compared with 68% (54 of 79 patients) for Xtandi alone. PSA 90% (decrease of at least 90% from baseline) response rates were 78% (65 of 83 patients) among those in the combination arm compared with 37% (29 of 79 patients) among those who received Xtandi alone.
In total, the ENZA-p study included 162 patients with mCRPC. Patients were randomly assigned 1:1 to two groups: 79 patients were in the Xtandi alone group and 83 patients in the Xtandi plus Pluvicto group.
Those included in the combination therapy arm underwent two doses with Pluvicto with SPECT with two additional doses for those with persistent PSMA-positive disease detected at 92-day follow-up. In total, 81% of patients in the combination arm received four doses of Pluvicto.
Emmett commented in the presentation, “We used two to four doses of (Pluvicto) in the ENZA-p trial, but two to six doses may further improve progression-free survival, particularly in those patients who have a high proportion of androgen persistent clones.”
Serious side effects were reported in 28 of 79 patients (35%) who received Xtandi alone, compared with 27 of 81 patients (33%) who received Xtandi with Pluvicto. Grade 4 or 5 side effects were reported among three of 79 patients (4%) in the Xtandi monotherapy arm, compared with eight of 81 patients (6%) in the combination arm.
In the presentation conclusion, Emmett noted, “I think this is going to become more important as we move this radiation treatment earlier in the disease paradigm to hormone sensitive prostate cancer. It (has) the potential to reduce toxicity by only administering if persistent PSMA-avid disease is present on the PSMA-PET or SPECT images.”
Emmett also added that there is planned follow-up of PFS and overall survival (OS, the time a patient lives following treatment) in the study until July 2024.
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