A recent study led by the Peter MacCallum Cancer Centre has revealed promising results for Lutetium-177 PSMA-617 (LuPSMA) therapy in treating patients with newly diagnosed prostate cancer that has already spread. The UpFrontPSMA trial indicates that adding LuPSMA to standard treatment significantly improves patient outcomes.
The phase 2 trial, a multicenter study conducted across 11 Australian hospitals, enrolled 130 participants with newly diagnosed metastatic prostate cancer. All patients received androgen deprivation therapy, and were then randomized to receive either chemotherapy alone (standard of care) or chemotherapy plus LuPSMA.
Improved Response Rates with LuPSMA
The addition of LuPSMA therapy to the standard treatment regimen led to a notable improvement in response rates. According to Associate Professor Arun Azad, who presented the findings at the ESMO Congress 2024 in Barcelona, undetectable PSA levels—a marker for prostate cancer—were achieved in 41% of patients receiving LuPSMA, compared to only 16% in the standard-of-care group at 48 weeks post-treatment.
"This is a remarkable result however before we can say this should change clinical practice, we need to see this replicated in a larger Phase III clinical trial and, thankfully, a trial like this is already underway globally," Azad noted.
Progression-Free Survival and Adverse Events
Benefits were observed across various progression-free survival measures. Importantly, the incidence of adverse events was similar in both treatment arms, with most adverse events linked to chemotherapy.
Trial Funding and Support
The UpFrontPSMA trial was funded by the Prostate Cancer Research Alliance (PCRA), involving Movember and the Australian Government's Medical Research Future Fund, with support from Novartis and a US Department of Defense grant. The trial also received support from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.
Lutetium-177 Production
The radioactive isotope Lutetium-177, crucial for LuPSMA therapy, is produced and supplied by ANSTO from its nuclear medicine precinct in Sydney. ANSTO provides 80% of Australia's nuclear medicines, which are used in the diagnosis, staging, and treatment of various medical conditions, including cancer.
Implications and Future Directions
Professor Michael Hofman, who leads the Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC) at Peter Mac, emphasized the significance of the results, stating, "The exciting results we have seen in the UpFrontPSMA trial validate the PCRA's approach of supporting high-risk, high reward clinical trials".
While the phase 2 results are promising, further validation in a larger phase 3 clinical trial is necessary before LuPSMA can be widely adopted as a standard treatment for newly diagnosed metastatic prostate cancer. A global phase 3 trial is already underway to confirm these findings.
