LOS ANGELES – Patients treated with prostate cancer vaccines prior to Pluvicto responded better to the treatment than non-vaccinated patients, according to a study presented May 30 at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) meeting.
The results suggest that “immunological priming” before radiopharmaceutical therapy may enhance clinical efficacy without impairing prostate antigen-specific T cell response, reported Bryce Wei Quan Tan, MD, of Singapore General Hospital.
"Prior vaccination against prostate cancer antigens may enhance the clinical efficacy of Lu-177 PSMA-617 [Pluvicto] therapy in metastatic castration-resistant prostate cancer," Tan said.
Bryce Wei Quan Tan, MD, of Singapore General Hospital, presented a study May 30 at SNMMI in Los Angeles.
Preclinical evidence has suggested that radiopharmaceutical therapy may trigger anti-tumor immune responses, raising the possibility of a benefit when combined with immune therapies, Tan noted. Vaccines against prostate cancer-specific antigens are immune therapies used to generate a T cell response against tumor cells. While prior work has examined pairing Pluvicto with immune checkpoint inhibitors, the question of whether immunological priming before therapy through vaccinations might improve outcomes had not been explored, he said.
To that end, Tan (at the University of Wisconsin at the time) and colleagues analyzed data from 109 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Pluvicto at the University of Wisconsin Carbone Cancer Center between January 2022 and January 2025, with follow-up through June 2025 and a median follow-up of 11.6 months. An additional 17 mCRPC patients who received at least one line of androgen deprivation therapy and one line of taxane-based chemotherapy, and who had prostate-specific membrane antigen (PSMA)-avid disease on PSMA PET/CT imaging, were included as controls.
Among the Pluvicto-treated patients, 19 had received prior vaccination in clinical trials targeting prostatic acid phosphatase (PAP) or PAP in combination with androgen receptor antigen. Primary outcomes were PSA50 response, defined as a 50% or greater decline in prostate specific antigen (PSA) and overall survival. Both vaccinated and non-vaccinated patients received a median of 4 cycles of 177Lu-PSMA-617, with no significant difference in cumulative dose between the two groups.
According to the results, 73.7 % of vaccinated patients achieved a PSA50 rate, compared to 55.6% in non-vaccinated patients and 23.5% in standard-of-care controls. Two-year overall survival was 47.6% in vaccinated patients versus 29.2% in non-vaccinated Pluvicto patients, and 23.5% in controls, a difference that reached statistical significance, Tan noted.
The retrospective design and modest sample size of the vaccinated subgroup limit the strength of the study, and Tan called for prospective studies examining the combination of vaccination and Pluvicto therapy.
"Prospective studies on the combination therapy of vaccinations and Lu-177 PSMA are warranted," he concluded.
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