Could Pluvicto Be a First-Line Systemic Treatment for Patients with Oligometastatic Hormone-Sensitive PCa?

New research suggests that the theranostic agent ¹⁷⁷Lu-PSMA-617 may provide a significant impact in treating oligometastatic hormone-sensitive prostate cancer (HSPC) and potentially deferring the use of androgen deprivation therapy (ADT).

For the randomized phase 2 BULLSEYE study, recently published in Lancet Oncology, researchers compared the use of ¹⁷⁷Lu-PSMA-617 (Pluvicto, Novartis) to a control group of active monitoring with deferred androgen deprivation therapy in a 56-patient cohort with biochemical recurrence of oligometastatic HSPC. All patients in the cohort had a prostate-specific antigen (PSA) level over 1 μg/L and a PSA doubling time of less than six months, according to the study.

In a study with a median 27-month follow-up, the researchers found that the median progression-free survival in the ¹⁷⁷Lu-PSMA-617 cohort was 25 months in comparison to five months in the control group. In the first 30 weeks of the trial, the study authors noted that only two of the 29 patients (7 percent) in the ¹⁷⁷Lu-PSMA-617 group exhibited disease progression in contrast to 27 out of 29 patients (93 percent) in the control cohort. The researchers also pointed out that those treated with ¹⁷⁷Lu-PSMA-617 had a 26-month median time to the next systemic therapy in comparison to six months in the control group.

In a recent interview with Diagnostic Imaging, James Nagarajah, M.D., a co-author of the study, emphasized the significant difference with ADT-free survival in the treatment group.

“That in my view is a very important finding in the study that you can really postpone hormone (therapy) for a significant time period,” maintained Dr. Nagarajah, an assistant professor in the Department of Radiology and Nuclear Medicine at the Radboud University Medical Center in Nijmegen, the Netherlands.

The study authors noted that 52 percent of patients treated with ¹⁷⁷Lu-PSMA-617 had a PSA90 response and seven patients had a complete biochemical response. Dr. Nagarajah pointed out that the crossover arm of the study yielded similar results in patients with greater metastatic disease.

“You can imagine that those patients do not belong to the currently used oligometastatic definition of a (maximum) five lesions on PSMA PET. They had more. And guess what? The response there was the same: 25 percent complete remission,” added Dr. Nagarajah.

(Editor’s note: For related content, see “New Study Shows High Efficacy and Patient Tolerance with 177Lu-PSMA-617 in Older Men with mCRPC,” “Study Emphasizes PSA and PSMA PET Tumor Volume Assessment for Predicting mHSPC Progression After Apalutamide and ADT” and “PSMA PET/CT Study Shows Mixed Results with Single Metastasis-Directed Radiotherapy for Oligometastatic PCa.”)