1217 - Eugonadal Progression-Free Survival Following Intensification of Metastasis-Directed Stereotactic Body Radiotherapy with Radioligand Therapy or Androgen Annihilation Therapy: A Comparison of Two Phase II Trials
Presenter(s)
E. D. Yu1, T. Romero2, M. Rettig3, H. Wilhalme4, J. Nikitas5, J. E. Juarez Casillas4, M. L. Steinberg6, R. E. Reiter7, C. Felix8, S. Parmisano6, K. Flores9, A. Sachdeva8, L. Valle8, K. Taparra8, A. E. Singer10, M. Allen-Auerbach11, J. Czernin11, N. Nichols12, J. Calais11, and A. U. Kishan8; 1UCLA David Geffen School of Medicine/UCLA Medical Center, Los Angeles, CA, 2Department of Medicine, University of California, Los Angeles, Los Angeles, CA, 3Department of Medical Oncology, University of California, Los Angeles, Los Angeles, CA, 4University of California, Los Angeles, Los Angeles, CA, 5Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 6Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 7Department of Urology, University of California, Los Angeles, Los Angeles, CA, 8Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, 9UCLA, Los Angeles, CA, 10Division of Hematology-Oncology, University of California Los Angeles Medical Center, Los Angeles, CA, 11Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 12VA and UCLA, Los Angeles, CA
Purpose/Objective(s):
The addition of 177Lu-PSMA-based radioligand therapy (RLT) to metastasis-directed stereotactic body radiotherapy (SBRT) has been shown to prolong eugonadal progression-free survival (euPFS) in men with oligorecurrent prostate cancer and is an attractive ADT-sparing approach. Whether an alternative strategy of adding androgen annihilation therapy (AAT; apalutamide plus abiraterone plus leuprolide) to SBRT would improve euPFS remains unknown. We hypothesized that these strategies would have similar euPFS, but SBRT+RLT would have less significant toxicity.Materials/Methods:
This analysis included patients receiving SBRT alone (n=18) or SBRT+RLT (n=20) on the LUNAR trial (NCT05496959) or SBRT+6 months of AAT (n=25) on the SATURN trial (NCT03902951) for M1 recurrences on PSMA PET after prior radical prostatectomy. Patients on the LUNAR trial who received SBRT or SBRT+RLT after prior RT, or for N1 recurrences after RP, were excluded to facilitate cross-trial comparisons. Inverse probability of treatment weighting (IPTW) analyses were performed to balance treatment groups, with weights derived from propensity scores as a age, PSA, PSADT, stage, lesion count, prior therapies, and interval from recurrence. The primary endpoint was euPFS with progression defined as new lesions on PSMA PET/CT and eugonadal status defined as testosterone >150 ng/dL. Toxicity burden was defined as experiencing at least 1 grade =3 adverse event.Results:
The median time to progression was 6 months, 19.4 months, and 21.7 months following SBRT, SBRT+RLT, and SBRT+AAT, respectively (p<0.001 for SBRT+RLT vs. SBRT and SBRT+AAT vs. SBRT). IPTW-adjusted analysis demonstrated comparable euPFS between SBRT+RLT and SBRT+AAT (HR 1.39, 95% CI 0.56–3.45, p=0.47), with consistent estimates across sensitivity models (HR ~1.3–1.5), despite shorter follow-up and a lower threshold to obtain PSMA PET imaging for patients treated with SBRT+RLT. Toxicity burden was numerically higher with SBRT+AAT, though this difference did not reach statistical significance (21% vs. 10%, p=0.5). Longer PSADT was independently associated with improved outcomes (HR 0.87 per month, p=0.018).Conclusion:
Both SBRT+RLT and SBRT+AAT improved euPFS over SBRT alone, while SBRT+RLT and SBRT+AAT achieved comparable euPFS. Given the numerical trend in grade =3 AEs favoring SBRT+RLT, in addition to the known quality of life impacts of hormonal therapy, SBRT+RLT appears to be a clinically attractive hormone-therapy sparing intensification strategy in men with oligorecurrent prostate cancer.