Reimagining Treatment Timelines: 177Lu-PSMA at Early Stages Ahead of Conventional Therapies
Radioligand therapy (RLT) utilizing 177Lu-PSMA gained initial approval in the USA as a final recourse once all other treatment options have been exhausted. However, quite a few ongoing trials are exploring the potential for deploying this therapy earlier in the course of the disease due to its demonstrated safety, efficacy, and relatively low incidence of side effects. In fact, radioligand therapy is very safe. A recent study has demonstrated that even 6 sessions are very well tolerated, what makes this treatment a viable option as a recurring therapy in case of recurrence.
While many of these studies are still ongoing, interim findings suggest that this therapy exhibits notable efficacy at earlier stages of the disease. It not only extends progression-free survival compared to conventional standard-of-care treatments such as anti-hormonal therapy or chemotherapy but also surpasses them in terms of preserving and enhancing patients' quality of life.
Here is a concise overview of key studies along with summaries of interim results and additional sources for more information:
ENZA-P Study
ENZA-P trial investigates the early use of 177Lu-PSMA in combination with androgen-pathway receptor inhibitor (ARPI) therapy (Enzalutamide). Phase II findings demonstrate robust anti-cancer activity, achieving significantly better results across all primary endpoints compared to Enzalutamide alone:
| Enzalutamide + 177Lu-PSMA | Enzalutamide alone | |
| PSA progression-free survival (PFS) | 13 months | 7.8 months |
| Radiographic PFS | 16 months | 12 months |
| PSA reduction >50% | 93% | 68% |
| PSA reduction >90% | 78% | 37% |
Moreover, the synergy between Enzalutamide and 177Lu-PSMA is notable, as Enzalutamide induces PSMA upregulation, particularly in PSMA-resistant cancer cells, thereby enhancing the efficacy of PSMA radioligand therapy. Adaptive dosing based on interim PSMA PET/CT scans employed in this trial aimed to minimize unnecessary radiation and toxicity without compromising effectiveness and it is yielding promising results.
PSMAfore Study
PSMAfore trial evaluated the use of 177Lu-PSMA in taxane-naïve patients, i.e. prior to chemotherapy. RLT more than doubled median radiographic PFS compared to androgen receptor-directed therapy (ARDT), from 5.6 to 12 months. It also demonstrated improvements in other clinically significant endpoints, including PSA response and quality of life measures. Results were presented at the 2023 ESMO annual meeting.
LuTectomy Study
LuTectomy trial examines the use of 177Lu-PSMA as neoadjuvant treatment before radical prostatectomy. Unlike external beam radiation, targeted radiation did not result in fibrosis, thereby avoiding any additional surgical complications. Initial results show a median PSA reduction of 49%, with 45% of patients achieving a PSA reduction >50%. The study is ongoing.
Several other promising trials are underway, such as PSMAddition and PSMA DC (delayed castration), which an aim to explore the use of 177Lu-PSMA for hormone-sensitive prostate cancer and before anti-hormonal therapy after radical prostatectomy respectively. Stay updated for upcoming announcements and subscribe to our channels on Instagram and Facebook.
Bibliography:
Video "Bringing Lutetium PSMA Earlier":
- ENZA P trial overview - min. 06:27 - 14:42
- PSMAfore trial overview - min. 23:24 - 27:50
- PSMAddition & PSMA DC introduction - min. 27:51 - 30:41
Safety and Efficacy of Extended Therapy with [ 177Lu]Lu-PSMA: A German Multicenter Study
