Patients with metastatic castration-resistant prostate cancer who were never treated with a taxane derived a progression-free survival benefit from treatment with Pluvicto.
Treatment with Pluvicto (177-Lu-PSMA-617) improved the duration of time when a patient’s disease did not progress with a favorable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC) who were taxane-naïve, according to recent results from a phase 3 trial.
Findings from the PSMAfore trial were presented at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain, by Dr. A. Oliver Sartor, a professor of medicine, urology and radiology at Mayo Clinic in Rochester, Minnesota.
Eligibility criteria included diagnosis of mCRPC, candidacy for androgen receptor pathway inhibitor (ARPI) change following one progression on prior ARPI treatment and having at least one PSMA-positive and no exclusionary PSMA-negative lesions. Of note, ARPIs are substances that keep prostate cancer cells from growing.
Patients were randomly assigned to Pluvicto or ARPI change (Zytiga [abiraterone]/Xtandi [enzalutamide]).
“Very, very importantly, those people on the hormonal therapies were able to crossover and to receive the lutetium if they in fact had met the (radiographic progression-free survival) end point,” Sartor said.
The study’s primary endpoint was progression-free survival (the length of time when a patient with cancer is alive without disease worsening), and the key secondary endpoint was overall survival (the time from the start of treatment when a patient with cancer is still alive).
A total of 234 patients each received either Pluvicto or ARPI change. Fifty-one patients (21.8%) in the Pluvicto arm discontinued treatment due to radiographic progression versus 146 patients (62.4%) in the ARPI change arm. Of the latter group, 123 patients (84.2%) crossed over to receive treatment with Pluvicto.
Baseline characteristics were similar between the Pluvicto and ARPI change groups. In the Pluvicto group, 119 patients (50.9%) had previously received Zytiga, and 94 patients (40.2%) had previously received Xtandi, whereas in the ARPI change group, 130 patients had previously received Zytiga (55.6%) and 84 patients (35.9%) had previously received Xtandi.
Sartor reported that the primary endpoint of progression-free survival was met, meaning that the results of the trial were similar of the expectations of the researchers before work started on the trial.
“No doubt about it, this is unequivocally a positive trial by the (radiographic progression-free survival) criteria. Quite positive,” Sartor commented.
Median progression-free survival was 12.02 months in the Pluvicto group versus 5.59 months in the ARPI change group.
Looking at radiographic response rates in measurable disease, objective response rate (the percentage of patients with a partial or complete response to treatment) was 50.7% in the Pluvicto group and 14.9% in the ARPI change group. Specifically, there was a 21.1% complete response rate (the disappearance of all signs of cancer from treatment) in the Pluvicto group versus 2.7% in the ARPI change group. Median duration of response (the time from when a patient first responded to treatment until progression or death) was 13.63 months in the Pluvicto group versus 10.05 months in the ARPI change group.
Confirmed PSA decrease of at least 50% was seen in 57.6% of patients in the Pluvicto group compared with 20.4% of patients in the ARPI change arm.
At a median follow-up of 12.72 months, median overall survival was 19.25 months in the Pluvicto group and at a median follow-up of 13.08 months, median overall survival was 19.55 months in the ARPI change group.
Regarding side effects, 77 severe or life-threatening side effects were observed (33.9%) in the Pluvicto group versus 100 (43.1%) in the ARPI change group. Forty-six serious side effects (20.3%) occurred in the Pluvicto group versus 65 (28.0%) in the ARPI change group. There were eight side effects leading to dose adjustment (3.5%) in the Pluvicto group versus 35 in the ARPI change group. Side effects occurring in at least 10% of patients in either arm included dry mouth, weakness, nausea, anemia, fatigue, constipation, decreased appetite, joint pain, COVID-19, diarrhea, back pain, vomiting, leg swelling and weight loss.
“In summary, PSMAfore met the primary (radiographic progression-free survival) end point with a very favorable adverse event profile, in taxane-naive patients with metastatic CRPC,” Sartor said.
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