Advanced treatment concepts of Lu-PSMA radioligand therapy beyond the VISION trial in metastatic castration-resistant prostate cancer

• Applicant: Dr. Adrien Holzgreve
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545058105

Prostate cancer is the most common cancer in men with a proportion of 22.7% of all cancers in men. Globally, the incidence is estimated to be approximately 1.6 million cases per year. Several factors contributed to decrease the disease-associated mortality over the last two decades including earlier diagnosis, greater understanding of high-risk mutations, better stratification of patient cohorts, and improved treatment quality in an evolving landscape of treatment options. However, prostate cancer currently remains the second-most fatal cancer in men, after lung cancer. Hence, prostate cancer is a major public health concern at the global scale, and further progress in developing treatment options is urgently needed to improve survival in this large cohort of patients. As demonstrated in the landmark VISION trial, prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using the beta-emitter Lutetium-177 (177Lu) proved to prolong survival and reduce symptoms compared to standard-of-care in patients with metastatic castration-resistant prostate cancer (mCRPC). This resulted in the approval of 177Lu-PSMA RLT by both the FDA and EMA in 2022. 177Lu-PSMA RLT is approved for the concomitant use with androgen deprivation therapy (ADT) in men previously treated with androgen receptor pathway inhibitors (ARSIs), and a taxan-based chemotherapy (either docetaxel or cabazitaxel). However, even after good responses to 177Lu-PSMA RLT, patients with mCRPC will uniformly relapse at some point after apparent delays in disease progression. Advanced prostate cancer remains a lethal disease with high mortality. There are very limited further treatment options. Hence, there is an unmet clinical need to establish new therapeutic strategies for this late stage of disease in mCRPC patients. This project investigates novel approaches of PSMA RLT in patients with mCRPC beyond the VISION trial. The main objective is to identify and shape advanced treatment concepts of PSMA RLT that have the potential to improve survival of mCRPC patients compared to the current standard-of-care. The project uses both prospective approaches and retrospective analyses that have the potential to culminate in future prospective clinical trials. These include adjusted time intervals in between RLT cycles and an increased number of total RLT cycles of 177Lu-PSMA RLT. Overall, there is a lack of high-class evidence for adapted and potentially more individualized treatment concepts of 177Lu-PSMA RLT beyond the VISION trial. Novel and individualized approaches of PSMA radioligand therapy proposed in this project will help to fill this gap and aim to provide personalized treatment options of PSMA radioligand therapy in patients with advanced prostate cancer.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Jeremie Calais