(UroToday.com) The advanced prostate cancer session at the 2021 American Urologic Association (AUA) annual meeting included a presentation by Dr. Scott Tagawa who discussed long-term follow-up and prognostic factor analysis among men with mCRPC who received 177Lu-PSMA therapy. PSMA-targeted radionuclide therapy has recently emerged as a promising treatment modality for advanced prostate cancer. PSMA may be targeted with antibodies (J591) or small molecule ligands (PSMA-617) labeled with the beta-emitting radionuclide lutecium-177. 177Lu-PSMA is a promising investigational treatment for men with mCRPC, however optimal selection and biomarkers remain to be defined. At today’s session, Dr. Tagawa and colleagues reported results of a combined analysis of men with mCRPC treated on sequential prospective clinical trials of PSMA-targeted 177Lu.
Patients treated on clinical trials from 2003 through 2020, with completion of treatment at least one year prior to analysis, were included in this study. Variables included type of PSMA-targeting, dose level, co-morbidities, CALGB (Halabi) prognostic risk group, PSMA imaging, circulating tumor cell counts, known DNA-repair alterations (germline and/or somatic), and receipt of FDA-approved subsequent therapies. PSMA imaging was scored based upon maximum tumor uptake relative to mean liver uptake on a scale of 0 to 4. Cox regression analysis and the Kaplan-Meier method were used to evaluate the association between variables and overall survival.
There were 76 men (60.8%) that received 177Lu-J591, and 49 men (39.2%) that received 177Lu-PSMA-617 included in this analysis. The median PSA was 50.14 ng/dL (range 0.66-2222.4), median age was 72 years (range 48-93), and the majority of patients were in the high Halabi risk category (57.6%). There were 49.6% of patients that received prior taxane chemotherapy, and 47.2% received prior abiraterone or enzalutamide. Overall, the median overall survival was 20.7 months (95% CI 17.4-24.0):
Furthermore, the median overall survival of 177Lu-J591 was 23.3 month (95% CI 21.1-32.6), whereas median overall survival was 16.7 months (95% CI 10.9-20.7) for 177Lu-PSMA-617. There were 26 men (20.5%) alive three years after treatment. Factors associated with longer survival included CALGB prognostic score (28.1 versus 16.9, p<0.0001), circulating tumor cell decline (24.9 versus 19.2, p=0.046), and receipt of subsequent therapy (28.1 versus 14.8, p=0.0002). Overall, those with stronger PSMA imaging uptake lived shorter, though when analysis was restricted to PSMA PET for those receiving 177Lu-PSMA-617, higher PSMA PET SUV (imaging score 4 versus 0-3) was associated with longer survival (18 vs. 10 months, p=0.015). Higher administered activity (22.1 versus 18.6, p=0.074) and DNA damage repair mutations (33.9 vs. 20.6, p=0.24) tended to have longer survival. On multivariable analysis, high Halabi risk group (HR 1.78, 95% CI 1.16-2.73) and total number of subsequent therapies (HR 0.79, 95% CI 0.71-0.89) retained their prognostic significance, with a trend for DNA damage repair mutations (HR 0.68, 95% CI 0.34-1.36).
Dr. Tagawa concluded his presentation of real-world utilization of radioligand therapy with the following take-home messages:
- For patients receiving PSMA-targeted 177Lu, CALGB prognostic risk group, and receipt of subsequent FDA-approved therapies may influence survival
- DNA damage repair mutations, higher administered activity, and circulating tumor cell count decline tended to be associated with longer survival
- Heterogeneity of PSMA imaging and treatment modalities in this dataset limit prognostic implications
Presented by: Scott Tagawa, MD, MS, FACP, Weill Cornell Medicine, New York, NY
Co-Authors: Michael Sun, Charlene Thomas, Benedict Ho, Junaid Niaz, Jones Nauseef, Joseph Osborne, Ana Molina, Cora Sternberg, David Nanus, Neil Bander
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.