3361 - Toxicity Assessment of Combined External Beam Radiation with [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy

Purpose/Objective(s):

The adoption of PSMA-directed radiopharmaceutical therapy (RPT) for metastatic prostate cancer (PC) has dovetailed with the expansion of metastasis directed EBRT. The interplay between the two modalities has not been systematically investigated. We aimed to characterize use patterns and composite toxicities experienced by patients who received both EBRT and RPT in proximity.

Materials/Methods:

We analyzed patients treated with ³1 cycle [177Lu]Lu-PSMA-617 and EBRT within 6 months of each other at a single institution. Toxicity was assessed by CTCAE v5.0 at the conclusion of the second treatment (i.e., last fraction of EBRT or last RPT infusion). Adverse events (AEs) were excluded if present prior to the second treatment. We performed multiple logistic regression testing to assess interactions between clinicodemographic factors and grade 3+ toxicities.

Results:

Between 02/2019-09/2024, we identified 81 metastatic PC patients who met study criteria with median age of 67 and a median pre-RPT PSA of 114. Patients received 141 courses of EBRT delivered to 189 unique sites, including spine 46% (87), other bone 37% (69), brain (dura/parenchyma) 6% (11), calvarium 6% (11), and other soft tissue 6% (11). 35% of sites (66) were treated with SBRT like fractionation (>5Gy/fraction in 1-5 fractions, excluding 8Gy x 1 palliative courses). 25% (20), 28% (23), 21%(17), 9%(7), 3% (2), and 15% (23) received 1, 2, 3, 4, 5, and 6 cycles of RPT, respectively.

With a median follow up of 4.2 months (range 0.1-34.2) from second treatment, we found 23 total relevant grade 3+ AEs with a median toxicity onset of 2.6 months (range 0.1-12.1). Such AEs included anemia with or without an additional cytopenia 26% (21) and GI bleed 3% (2) in the setting of radiation to lumbar/sacral spine metastases. On multiple logistic testing, number of unique EBRT courses within 6 months was associated with incidence of grade 3 toxicities (OR 2.7, 95% CI 1.05-8.61).

Conclusion:

In the setting of combined EBRT and RLT, we observed a slightly higher rate of grade 3 anemias than expected with [177Lu]Lu-PSMA-617 alone (26% vs ~13%). Toxicity was associated with number of unique RT courses within 6 months. Despite these findings, our data suggests a low rate of additive severe toxicities when EBRT and RPT are delivered in proximity, justifying on-going combination trials.