Identifying Genomic Features, Post-therapeutic Predictors of Response to Lu-177 PSMA-617 for mCRPC

New research presented at the Society of Nuclear Medicine and Molecular Imaging Annual Meeting highlighted the real-world outcomes of Lu-177 PSMA-617 treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) and identified genomic features as well as post-therapeutic single-photon emission computed tomography/computed tomography (SPECT/CT) parameters as predictors of response.

Harshad R. Kulkarni, MD, FANM, of BAMF Health, and colleagues designed a retrospective, single-center pilot study that sampled 53 patients with mCRPC from August 2022 to January 2023 who were treated with 1 to 4 cycles of Lu-177 PSMA-617 according to National Comprehensive Cancer Network guidelines and after prior confirmation of prostate-specific membrane antigen expression.

With an interval of 6 weeks between cycles, 5 patients underwent 4 cycles, 9 patients underwent 3 cycles, and 14 patients underwent 2 cycles, whereas 25 patients underwent 1 cycle each of treatment. Researchers noted that all patients underwent post-therapeutic SPECT/CT 1 to 4 days after treatment to assess post-therapeutic biodistribution and molecular therapy response.

The maximum standardized uptake value (SUV_max) and total molecular tumor volume (MTV) were analyzed after every cycle of therapy. Hematological status, renal and hepatic function, and serum prostate-specific antigen (PSA) levels were documented before and after therapy.

Results of the analysis showed that among the 35 patients who had at least 1 follow-up after 1 or more cycles of therapy, 11 patients experienced partial remission, 14 patients had stable disease, and 10 patients had disease progression. Early identification of progression resulted in discontinuation of treatment after 2 cycles in 4 patients and after 3 cycles in 6 patients.

Researchers found that among the patient responders, 54.5% had “maximum” frequency of ATM mutations identified. Treatment was well tolerated in all but 4 patients, who had reversible nausea and vomiting. Of note, 2 of the patients with vomiting had ATM mutations and 3 of the patients had residual low-volume disease.

Furthermore, researchers reported that the percentage changes in PSA correlated best with percentage changes in MTV, but not with SUV_max, on pre- and post-therapy SPECT/CT.

In their concluding remarks, authors stated that “ATM mutations and reduction in molecular tumor volume on SPECT/CT appear to predict a favorable response to treatment with Lu-177 PSMA-617,” adding that future clinical trials need to examine the integration of different features with individual post-therapeutic dosimetry for further personalization of care.