(UroToday.com) The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Michael Sun discussing PSMA-alpha targeted radionuclide therapy with or without prior PSMA-beta targeted radionuclide therapy. PSMA-targeted radionuclide therapy has included either beta-emitters (Lutetium-177) or alpha-emitters (Actinium-225), with alpha-emitting radionuclides having significantly higher linear energy transfer over shorter range versus beta-emitters. Importantly, responses have been observed in patients treated with 225Ac-J591 after 177Lu-PSMA, supporting sequential administration. However, there are no known data-driven normal organ dose limits for radionuclide therapy, with putative limits extrapolated from external beam radiotherapy. At the 2023 ESMO annual congress, Dr. Sun and colleagues evaluated baseline demographics and prior exposures for association with outcomes following treatment with 225Ac-J591.
Patients treated on prospective clinical trials of 225Ac-J591 were retrospectively analyzed with a focus on efficacy and adverse events with prior therapies. Kaplan-Meier method was used for time to event endpoints (OS and PFS). Overall, there were 21 patients with prior beta-therapy and 64 patients with no prior beta therapy. Baseline characteristics were as follows:
Adverse events in patients with and without prior 177Lu-PSMA were generally comparable:
There were no differences in the frequency of nausea, xerostomia, or pain seen with/without prior 177Lu-PSMA, but grade 2 fatigue was more common in those with prior 177Lu-PSMA (48% vs 17%, p=0.023). Within limits of a small sample size, higher exposure of sequential 177Lu-PSMA, radium-223, external beam radiotherapy, and 225Ac-J591 was associated with higher rates of grade 4 thrombocytopenia (p = 0.031). There was no treatment-related renal failure observed with short-term follow up +/- prior 177Lu-PSMA. Similar adverse event trends were seen for grade 4 hematologic adverse events with prior radium-223 exposure, and those with ≥2 lines of chemotherapy may be more likely to have grade 4 hematologic adverse events. There was no significant difference in efficacy of 225Ac-J591 with/without prior 177Lu-PSMA with regards to PSA50: 52% vs 58%:
Additionally, there were no significant differences in PFS (4.03 months vs 5.07 months, p = 0.16) or in OS (16.4 months vs 17.3 months, p = 0.80) in patients with/without prior 177Lu-PSMA:
Finally, there were no significant efficacy differences based upon prior radium-223: bPFS 3.9 vs 4.8 months (p = 0.39), OS 10.7 vs 17.3 months (p = 0.12), PSA50 (53% vs 57%; p = 0.80)
Dr. Sun concluded his presentation by discussing PSMA-alpha targeted radionuclide therapy with or without prior PSMA-beta targeted radionuclide therapy with the following concluding statements:
- In one of the largest prospective cohorts to date, alpha-targeted radionuclide therapy with 225Ac-J591 is associated with a minority of patients having high grade adverse events and retains efficacy following beta-targeted radionuclide therapy and radium-223
- Risk of grade 4 thrombocytopenia appears highest in those with prior 177Lu-PSMA, radium-223, and external beam radiotherapy, but high-grade events are rare
- New examination of organ dose-limits with targeted radionuclide therapy is warranted
Presented by: Michael Sun, MD, Weill Cornell Medical College, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.