(UroToday.com) The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Kambiz Rahbar discussing safety and effectiveness outcomes of 177Lu-PSMA therapy in patients with prior treatment with radium-223. Radium-223 is an established targeted alpha therapy with a good safety profile that prolongs overall survival (OS) and improves quality of life in patients with bone-predominant mCRPC.1 177Lu-PSMA, a beta particle emitting therapy, has shown an acceptable safety profile and prolonged OS in heavily pretreated PSMA positive mCRPC patients,2 including taxane-based chemotherapy and radium-223.3 Previous studies suggest feasibility of using 177Lu-PSMA after radium-223 with an acceptable safety profile. At the 2022 ESMO meeting, Dr. Rahbar and colleagues investigated the safety and effectiveness of 177Lu-PSMA in patients with mCRPC and prior radium-223 in the RALU study.
RALU is a retrospective medical center chart review of patients with radium-223 prior to 177Lu-PSMA in German nuclear medical centers:
Patients were >=18 years of age with a confirmed diagnosis of mCRPC and a prior history of radium-223 therapy who received >=1 cycle of 177Lu-PSMA. Safety and effectiveness were evaluated in all patients and by the treatment sequence: radium-223 followed by chemotherapy followed by 177Lu-PSMA, or chemotherapy followed by radium-223 followed by 177Lu-PSMA.
Overall, 133 patients were included in this analysis, with the following treatment sequence groups:
Before starting 177Lu-PSMA, the proportion of patients with an ECOG performance status of 0, 1, or 2 was 0%, 62%, and 38%, respectively. Median PSA was 285.5 ng/ml and median alkaline phosphatase (ALP) was 146.0 U/L. There were 56% of patients that had received ≥4 life prolonging therapies, including abiraterone (71%), enzalutamide (70%), docetaxel (74%), and cabazitaxel (23%); 71% of patients had received six radium-223 injections. All patients had bone metastases and 27% had visceral metastases. Baseline characteristics before starting 177Lu-PSMA are as follows:
There were 73% of patients that received 1–4 177Lu-PSMA cycles and 27% received ≥5 cycles. Safety was as follows:
During 177Lu-PSMA treatment, PSA50 response occurred in 42% of all patients, 46% of the radium-223 followed by chemotherapy followed by 177Lu-PSMA patients, and 36% of the chemotherapy followed by radium-223 followed by 177Lu-PSMA patients. ALP50 response occurred in 9% of all patients and was similar in the radium-223 followed by chemotherapy followed by 177Lu-PSMA and chemotherapy followed by radium-223 followed by 177Lu-PSMA groups (6% vs 6%, respectively):
Median OS from the start of 177Lu-PSMA treatment was 13 (95% CI 11–16), 12 (95% CI 9–15), and 14 (95% CI 9–17) months in all patients, radium-223 followed by chemotherapy followed by 177Lu-PSMA, and chemotherapy followed by radium-223 followed by 177Lu-PSMA groups, respectively.
Dr. Rahbar concluded this presentation discussing safety and effectiveness outcomes of 177Lu-PSMA therapy in patients with prior treatment with radium-223 with the following take-home messages:
- In patients for whom radium-223 had been used as part of routine disease management, subsequent 177Lu-PSMA therapy was clinically feasible and well tolerated, with acceptable myelosuppression rates. Survival outcomes in patients who received the radium-223/177Lu-PSMA sequence were similar to those reported in previous real-world studies and the phase 3 VISION trial
- Incorporation of radium-223 in common therapy sequences for mCRPC is feasible, including taxane-based chemotherapy in between radium-223 and 177Lu-PSMA, without alteration of safety profile or overall survival from the start of 177Lu-PSMA
Presented by: Kambiz Rahbar, MD, Department of Nuclear Medicine, University of Münster Medical Center, Muenster, Germany
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 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.
References:
- Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
- Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
- Heck MM, Tauber R, Schwaiger S, et al. Treatment outcome, toxicity, and predictive factors for radioligand therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant prostate cancer. Eur Urol. 2019 Jun;75(6):920-926.