The UpFrontPSMA study, led by the Peter MacCallum Cancer Centre, has revealed promising results for Lutetium-177 PSMA-617 (LuPSMA) therapy in patients with newly diagnosed metastatic prostate cancer. The study, presented at the European Society for Medical Oncology (ESMO) Congress 2024 and published in The Lancet Oncology, suggests that LuPSMA, previously effective in late-stage prostate cancer, can also dramatically improve outcomes in earlier stages of the disease.
The phase 2 trial involved 130 participants from 11 Australian hospitals, all of whom had newly diagnosed prostate cancer that had spread. Participants received androgen deprivation therapy and were randomized to receive either chemotherapy alone (standard of care) or chemotherapy plus LuPSMA.
Improved Response Rates with LuPSMA
Associate Professor Arun Azad, who presented the results at ESMO 2024, highlighted the significant improvement in response rates when LuPSMA was added to the standard of care. "We looked for undetectable PSA - a marker for prostate cancer - at 48 weeks after treatment and this was achieved in 41% of patients who received LuPSMA compared to just 16% for the standard-of-care," Azad explained.
Progression-Free Survival
The study also observed benefits across a range of progression-free survival measures. Importantly, adverse events were similar in both treatment groups and primarily linked to chemotherapy, suggesting that the addition of LuPSMA did not significantly increase treatment-related toxicity.
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.
Future Directions
While the results are promising, Associate Professor Azad emphasized the need for confirmation in a larger phase 3 clinical trial before clinical practice changes. A global trial is already underway to further evaluate these findings.
Professor Michael Hofman, who leads the Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC) at Peter Mac, noted that the results validate the PCRA’s approach of supporting high-risk, high-reward clinical trials.
The radioactive isotope Lutetium-177, which is essential for LuPSMA therapy, is produced and supplied by ANSTO from its nuclear medicine precinct in Sydney. ANSTO provides 80% of Australia’s nuclear medicines used in the diagnosis, staging, and treatment of various medical conditions, including cancer.
