ASCO 2021: Long-Term Adverse Events (AE) in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Receiving Prostate-Specific Membrane Antigen (PSMA)-Based Targeted Radionuclide Therapy (TRT)

( There has been a proliferation in treatment options for patients with metastatic castration resistant prostate cancer (mCRPC) in the last 10 years. While the most commonly utilized approaches in prostate cancer are cytotoxic chemotherapy or target the androgen-axis, recently, theranostic treatment with the PSMA-targeting radioligand therapy (TRT) has demonstrated promising activity among pre-treated individuals with mCRPC. Expected short-term toxicities associated with PSMA-TRT include dose-dependent myelosuppression and xerostomia. In the Prostate, Testicular, Penile Poster session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Michael Sun presented data assessing long-term effects of PSMA-TRT on marrow, renal, and liver function.

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