Sequencing Radioligands Appears to be Safe, Viable Strategy for mCRPC

Radionuclide 177Lu-PSMA-617 (Pluvicto) yielded comparable overall survival (OS) outcomes and tolerability whether administered within 6 months or more than 6 months after radium-223 in patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC), according to findings from the RALU study presented at the 2023 Genitourinary Cancers Symposium.

"The question RALU set out to ask is whether it is safe to sequence two radionuclide therapies, an alpha and a beta emitter, in patients with mCRPC," according to an expert from University Hospital of Münster in Germany.

“The rationale for the RALU study is that the radium and lutetium PSMA- 617 have both demonstrated overall survival benefit and acceptable safety in patients with mCRPC,” said Kambiz Rahbar, MD, department of Nuclear Medicine, University Hospital of Münster in Germany, said while presenting the findings at the symposium.

"The question RALU set out to ask is whether it is safe to sequence two radionuclide therapies, an alpha and a beta emitter, in patients with mCRPC.”

Patient Characteristics

The study analyzed outcomes from patients with mCRPC who were treated with 177Lu-PSMA-617 within 6 months of radium-223 treatment (group 1; n=42) and those who were treated with 177Lu-PSMA-617 6 or more months after radium-223 treatment (group 2; n=90).

Median age was 72 and 74 years in group 1 and group 2, respectively. Regarding performance status, 57% and 63%, respectively, had and EGOG status of 1, while 43% and 37% had an ECOG status of 2. Median prostate-specific antigen (PSA) values were 366 and 268 ng/ml, and median alkaline phosphatase (ALP) values were 133 and 149 U/L.

Forty percent and 64% of patients in group 1 and group 2, respectively, had 4 or more prior life-extending therapies, with all patients having prior radium-223 treatment. The most common other therapies were: abiraterone (60% in group 1 and 77% in group 2), enzalutamide (50% and 78%), docetaxel (71% and 76%) and cabazitaxel (17% and 26%).

Visceral metastasis was present in 24% of patients in group 1 and 29% of patients in group 2 before undergoing therapy with 177Lu-PSMA.

RALU Outcomes

Study outcomes showed that between the start of 177Lu-PSMA therapy to 30 days after the last dose, 71% and 82% of patients in groups 1 and 2, respectively, experience any-grade treatment-related adverse events (TRAE), with the most common being fatigue (12% and 7%), nausea (12% and 8%) and dry mouth (7% and 18%). Grade 3-4 TRAEs, excluding laboratory abnormalities, were experienced in 36% of patients in group 1 and 24% of patients in group 2.

Treatment-related deaths occurred in 2% of patients in group 1 and 4% of patients in group 2, with TRAEs leading to dose delays in 10% and 9% of patients in group 1 and 2, respectively.

Survival outcomes showed no statistically significant difference in median OS between group 1 and group 2. In group 1, median OS from the start of 177Lu-PSMA treatment was 12.0 months (95% CI, 8.8-19.9), while it was 13.2 months (95% CI, 10.0-15.9) in group 2.

During therapy with 177Lu-PSMA, PSA responses of 50% or more occurred in 53% of patients in group 1 and 39% of patients in group 2, with ALP responses of 30% or more occurring in 28% and 14% of patients, respectively.

“In conclusion, we can say that these data can show that treating patients with lutetium within 6 months of completing radium was clinically feasible and well tolerated.”

Reference

Rahbar K, Essler M, Eiber M, et. al. Time interval between radium‑223 (223Ra) therapy and Lutetium-177–prostate-specific membrane antigen (177Lu-PSMA) treatment and outcomes in the RALU study. Presented at: 2023 ASCO GU Cancers Symposium. February 16-18, 2023. San Francisco, CA.