177Lu-PSMA-I&T Generates PSA Responses With Tolerable Safety in mCRPC

Derya Tilki, MD

Treatment with lutelium 177 PSMA-I&T (¹⁷⁷Lu-PSMA-I&T) radioligand therapy led to prostate-specific antigen (PSA) declines with an acceptable toxicity profile in patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings from a study assessing the antitumor efficacy and safety of ¹⁷⁷Lu-PSMA-I&T presented at the 2023 American Urological Association Annual Meeting.¹

Clinical progression-free survival following the first cycle of radioligand therapy was 6.3 months, and overall survival following the first cycle was 21.4 months.

“PSMA-targeted radioligand therapy with [¹⁷⁷Lu-PSMA-617] Is associated with prolonged overall survival in patients with metastatic castration-resistant prostate cancer, but data regarding the oncological efficacy and toxicity of [¹⁷⁷Lu-PSMA-I&T] are limited,” explained study author Derya Tilki, MD, visiting faculty at Koç University in Istanbul, Turkey, and urologist at Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Germany.

For the study, a total of 33 patients with mCRPC received a total of 88 cycles (median, 2 cycles; range, 1-7 cycles), of ¹⁷⁷Lu-PSMA-I&T.

“¹⁷⁷Lu-PSMA-I&T was given with a median activity of 7.5 GBq (IQR: 6.7 – 8.1) per cycle,” wrote the authors in their abstract.

Oncological outcomes measured included clinical progression-free survival, time interval from the first radioligand therapy cycle to any radiological or biological progression.

“We assessed response according to PSA changes and imaging response,” Tilki said.

The investigators utilized Common Toxicity Criteria for Adverse Events (CTCAE) to assess toxicity.

Median patient age at the time of first radioligand therapy cycle was 71.6 ± 10.7 years. PSA response of any amount was seen in 22 patients (69%), at least 30% in 18 patients (56%), at least 50% in 11 patients (33%), and at least 90% in 6 patients (33%).

Regarding toxicities, nephrotoxicity was observed in 4 cases, with CTCAE grade of 1 to 2 in 2 patients, 2 to 3 in 1 patient, and 3 to 4 in 1 patient. Hematotoxicity was experienced in 6 patients (18.2%). The investigators also reported 6 cases of grade 1/2 myelotoxicity (18.2%) and grade 3/4 myelotoxicity in 3 cases (9.1%).

Limitations of the study included its retrospective nature as well as the varying histories of the patients included in the study, according to Tilki.

“These are one of the few data for PSMA radioligand therapy with PSMA i&T in contrast with PSMA 617, and the toxicity profile is very similar [to that of] PSMA-617,” Tilki said in her presentation of the data.

Reference

Demirkol MO, Esen B, Sen M, et al. Radioligand therapy with 177Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer: oncological outcomes and toxicity profile. Presented at: American Urological Association Annual Meeting, April 28-May 1, Chicago, Illinois. Abstract MP11-07