ASCO 2021: VISION Study Results – Phase III Study of Lutetium-177-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

( In this presentation, Dr. Michael Morris presented the results of the phase 3 VISION trial evaluating the radiopharmaceutical lutetium-PSMA (Lu-PSMA) in patients with metastatic castration-resistant prostate cancer.

Prostate-specific membrane antigen (PSMA) is a promising molecular target to both imaging and targeted therapy in prostate cancer. PSMA is a transmembrane carboxypeptidase that is highly expressed on the surface of prostate cancer cells including metastatic lesions, and is only expressed on a few normal tissues such as the salivary and lacrimal glands. Prior studies have confirmed that PSMA-bound imaging molecular are highly specific for PET-based imaging of prostate cancer. The PSMA-617 molecule targets surface PSMA with high affinity, and when conjugated to lutetium-177, allows for receptor-mediated endocytosis of this beta-emitting radiation particle into target cells.

The VISION trial randomized patients with at least one PSMA-PET positive metastatic lesion and no PSMA-negative metastatic lesions above a certain threshold (see below) to receive either Lu-PSMA plus ongoing standard of care or standard of care. The key eligibility criteria are shown below. The standard of care treatment arm was decided upon prior to randomization of a patient, and excluded chemotherapy, immunotherapy, or radium-223 given the unknown safety of combining Lu-PSMA with these agents. Most patients received either the alternative androgen receptor pathway inhibitor if they had not received


Patients in the Lu-PSMA treatment arm received 4 cycles of drug, with an option to extend to 6 cycles if disease response was seen but there was no complete response.


The study had two prespecified alternative primary endpoints, meaning that the study would be positive if either the radiographic progression free survival or overall survival endpoints were met. The statistical plan for the trial is illustrated below.


Most patients who met other eligibility criteria also had a positive PSMA-PET scan (87%). Importantly, within the first 9 months of enrollment, there was a 56% dropout rate in the standard of care control arm. In discussion with the FDA, enhanced study site education and enrollment caps were implemented, which brought the dropout rate down to approximately 16%. Given the change in enrollment education, accrual for the rPFS endpoint began afresh to reduce bias, but OS was still assessed in all randomized patients as this was felt to be immune to bias from the protocol change. This resulted in 581 patients eligible for rPFS assessment and 831 patients eligible for OS assessment.

Patient characteristics were well-balanced, as were the types of previous cancer treatments.


With regards to the alternate primary endpoints, Lu-PSMA prolonged overall survival from a median of 11.3 months to 15.3 months, conferring a hazard ratio of 0.62 (p < 0.001) for death. This OS benefit was seen across all 831 patients, as well as the 581 patients analyzed for rPFS.


This survival benefit was generally consistent across subgroups.


The rPFS endpoint was also positive, improved from 3.4 months to 8.7 months (HR 0.40, p < 0.001) in the primary analysis cohort and this trend was generally consistent across subgroups.


With regards to overall response, 9.2% of patients had a complete response and 41.8% of patients had a partial response with Lu-PSMA by RECIST v1.1 criteria. 46% of patients had a decrease in PSA by over 50%, and 33% of patients had a PSA decrease by over 80%. Half of patients in the Lu-PSMA arm received the option fifth and sixth cycles of therapy.

Post-protocol therapies are shown below. Slightly higher rates of patients in the standard of care control arm went on to receive additional therapies, suggesting that the benefit of Lu-PSMA is not related to subsequent treatment.



More treatment related adverse events were noted with Lu-PSMA



Dr. Morris concluded that adding Lu-PSMA to certain standard of care treatment options in pre-treated metastatic castration resistant prostate cancer extended overall survival in patients and delayed radiographic progression. Overall, this treatment was relatively well tolerated, and he argued that these findings justify Lu-PSMA as a new treatment option in patients with mCRPC.

Presented by: Michael J. Morris, MD, Prostate Cancer section head and GU medical oncologist at the Memorial Sloan Kettering Cancer Center, New York, New York.

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021