Lutetium-177–PSMA-617 (Lu-177–PSMA-617)—an investigational radioligand therapy—significantly improved radiographic progression-free survival and overall survival when added to standard of care compared with standard of care alone for men with metastatic castration-resistant prostate cancer whose disease had progressed on other lines of treatment. These results from the phase III VISION trial were presented by Michael Morris, MD, and colleagues at the 2021 ASCO Annual Meeting (Abstract LBA4).

Lu-177–PSMA-617 plus the standard of care resulted in a median of 8.7 months for radiographic progression-free survival vs 3.4 months with the standard of care alone. Overall survival was also extended to 15.3 months with Lu-177–PSMA-617 vs 11.3 months with the standard of care alone.

Michael Morris, MD

“In patients with metastatic castration-resistant prostate cancer whose cancer had progressed after chemotherapy and androgen receptor pathway inhibitors, Lu-177–PSMA-617 prolonged life and delayed time to disease progression on scans. These findings warrant Lu-177–PSMA-617 as a new treatment option for metastatic castration-resistant prostate cancer, pending U.S. Food and Drug Administration review,” stated presenting author Dr. Morris, Head of the Prostate Section at Memorial Sloan Kettering Cancer Center, New York.

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related deaths in the United States. Although a number of treatment options are available for metastatic castration-resistant prostate cancer, most patients experience disease progression and need several lines of therapy, and durable remissions are uncommon with each new line of therapy.

PSMA (prostate-specific membrane antigen) is highly expressed on prostate cells across the disease spectrum and is an excellent target for treatment. Positron-emission tomography (PET)-PSMA scans are used to detect occult cancers in patients with advanced disease whose bone scans and computed tomography scans appear normal. Targeting PSMA with a radioligand such as Lu-177–PSMA-617 is a novel treatment approach, and hopes were high in the prostate cancer community that such a method would be successful.

“Lu-177–PSMA-617 targets PSMA with high affinity. It releases its payload of beta radiation into the prostate cancer cell, which is exposed to lethal radiation and dies,” Dr. Morris explained.

VISION Details

VISION enrolled patients with metastatic castration-resistant prostate cancer and a PSMA-positive PET scan whose disease had progressed after previous treatment with an androgen receptor pathway inhibitor and one to two taxane chemotherapy regimens. Patients (n = 831) were randomly assigned 2:1 to receive the standard of care (determined by treating physician) plus Lu-177–PSMA-617 or the standard of care alone. The experimental radioligand pharmaceutical was given for four cycles every 6 weeks; responders could have an extra two cycles.

There were two primary endpoints: overall survival and radiographic progression-free survival. The analysis of radiographic progression-free survival focused on 531 patients; the overall survival analysis was based on 831 patients.

Median follow-up was 20.9 months at the time of data cutoff. Lu-177–PSMA-617 plus the standard of care significantly improved radiographic progression-free survival by 60% vs the standard of care alone: median radiographic progression-free survival was 8.7 months vs 3.4 months, respectively (P < .001). Overall survival was also significantly improved—by 38%—with Lu-177–PSMA-617 plus the standard of care vs the standard of care alone: median of 15.3 months vs 11.3 months (P < .001).

All key secondary endpoints were also statistically improved for the experimental arm vs the control arm.

However, more treatment-emergent adverse events were observed in patients in the experimental arm: 53% vs 38% with the standard of care alone. Among patients receiving Lu-177–PSMA-617, high-grade bone marrow suppression was observed in about 25%, high-grade anemia in 13%, low platelet count in 8%, and dry mouth (not high grade) in 39%.

“Lu-177–PSMA-617 is currently being studied in earlier stages of prostate cancer,” Dr. Morris noted.

Commentary

At a press conference where these findings were discussed, ASCO President Lori J. Pierce, MD, FASTRO, FASCO, commented: “This trial is clearly important. These men had disease progression, even with very low levels of testosterone. Lu-177–PSMA-617 is an alternative therapy delivered directly to the prostate cancer cells, and survival was significantly improved. The use of Lu-177–PSMA-617, if it gets regulatory approval, could become an important new treatment option for patients with metastatic castration-resistant prostate cancer.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.