To do so, the authors examined men treated on prospective clinical trials of PSMA-TRT from 2003 through 2020 who had at least six months of follow-up were included. They collected information including treatment, comorbidities, baseline, and most recent renal, liver, and marrow function, along with respective short-term (< 6 months) and long-term toxicities. Adverse events (AEs) were graded using CTCAE version 5 and attribution was assessed with most recent clinical follow-up. The authors used multivariable logistic regression to examine predictors of long-term AEs.
The authors identified 119 patients. Their median PSA was 45.8 ng/dL (range 0.66 – 7168) and the majority were Halabi high risk (55%). 77% had received prior taxane chemotherapy and 9% had received prior radium-223. In terms of PSMA-targeting radioligand therapy, 71 (59.7%) patients received 177Lu-J591, 30 (25.2%) received 177Lu-PSMA-617, 11 (9.2%) received 225Ac-J591, and 7 (5.9%) received 90Y-J591. At index, the median age was 71 months.
Over a median follow-up of 18 months (range 6-133), long-term (most recent) AEs were typically graded 1 through grade 3 and 4 events did occur, as highlighted in the following table.
However, it warrants mention that a majority of AEs were attributed to alternate etiologies. In particular, only two Gr ≥3 AEs were attributed to possibly being related to PSMA-TRT: one case of Gr 4 renal dysfunction (creatinine elevation) and one case of Gr 3 ALT elevation. On multivariable logistic regression, alpha-TRT was associated with hepatic AEs (OR 4.38, p = 0.047), and there was a trend towards an association between higher Charlson Comorbidity scores and hematologic AEs (OR 1.27, p = 0.1).
Following TRT, most patients receive further therapy (median 2 subsequent lines, range 0-10) including abiraterone/enzalutamide (33%), docetaxel (38%), cabazitaxel (21%), platinum-based chemotherapy (23%), radium-223, sipuleucel-T, and additional PSMA-TRT.
The authors conclude that in this the largest analysis to date of long-term AEs in patients who have received PSMA-TRT, long-term effects on renal, liver, and marrow function are infrequent. Further, the majority of patients are able to receive further lines of therapy.
Presented by: Michael Sun, MD, Internist, New York-Presbyterian Hospital-Weill Cornell, New York, NY
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021