There are several questions surrounding PSMA imaging that continue to evolve. These include whether preoperative staging in high-risk patients can be improved using PSMA. Can signs of disease be detected in early biochemical recurrence using this novel modality? It's not clear whether we can adequately guide focal therapy for oligometastatic disease with PSMA imaging? We would also like to know whether we can image response to therapy in treated lesions. Lastly, we want to know whether we can utilize PSMA targeted imaging to select patients that would benefit from PSMA targeted therapy.
Lu-PSMA-617 is a PSMA-targeted radioligand therapy (Figure 1).
Figure 1 :
In a retrospective analysis of 167 patients with metastatic castrate-resistant prostate cancer treated with 177LuPSMA-617 were classified as either taxane-pretreated or naïve.1 These two groups of patients were compared. The median overall survival was 10.7 months for pretreated patients compared to 27.1 months for patients not pretreated. A similar advantage was seen in radiographic progression-free survival. PSA response was seen in 57% and 40% of patients not pretreated and pretreated patients, respectively.
Dr. Pienta states that it is estimated that 40% of patients treated with 177LuPSMA-617 will respond with a more than 50% decrease in their PSA. Furthermore, it is estimated that 70% of patients will have any PSA decrease with this type of treatment.
A large, randomized, controlled trial (The VISION trial, NCT03511664) is assessing 177Lu-PSMA-617 and is currently accruing patients. This is an international Phase III trial that enrolled approximately 750 patients with progressive metastatic castration-resistant prostate, who received 1-2 lines of previous taxane therapy as well as previous novel hormonal therapy (e.g., abiraterone, enzalutamide). 68Ga-PSMA PET positivity at baseline was mandated for eligibility for this trial. The randomization was 2:1 177Lu-PSMA-617 plus best standard of care vs. non-chemotherapy best standard of care. The primary endpoint will be overall survival, and a positive result of this trial will have a high potential to lead to a new regulatory approval.
In conclusion, there are multiple indications for diagnostic PSMA-based imaging that have been extensively explored. We are currently just starting to understand PSMA-targeted PET findings as imaging biomarkers. PSMA-based therapy is effective and well-tolerated. Increasing the effectiveness, but also protecting against toxicities, will be the key next steps. The awaited results of the VISION trial will be published in 2021.
Lastly, there are also other multiple clinical trials assessing 177Lu-PSMA-617 that are actively accruing patients:
- LuPARP trial - 177Lu-PSMA-617 with olaparib (NCT03874884)
- PRINCE trial – 177Lu-PSMA-617 with pembrolizumab (NCT03658447)
- Antibody with small molecular combination - 177Lu-PSMA-617 with 177Lu-J591 (NCT03545165)
- Lu-PSMA trial - Radiometabolic 177Lu-PSMA-617 (NCT03454750)
- Fractionated 177Lu-PSMA-617 trial (NCT03042468)
Presented by: Kenneth Pienta, MD, Director of Research, The James Buchanan Brady Urological Institute, Professor of Urology, Johns Hopkins University School of Medicine
Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020
1. Barber TW, Singh A, Kulkarni HR, Niepsch K, Billah B, Baum RP. Clinical Outcomes of (177)Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2019;60(7):955-62.
177LU-PSMA-617 in the Treatment of Patients with Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer - Oliver Sartor