Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks

Abstract

Purpose [ 177 Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC). Here, we aimed to estimate the results of PSMA-RLT in terms of response, progression-free survival (PFS), and overall survival (OS) in patients receiving a highly standardized treatment regimen due to mCRPC. The toxicity of PSMA-RLT has also been evaluated. Patients and methods Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0-4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment. Results The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7-4563 μg/L, P < 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks, P < 0.0001) and OS (median survival not reached vs. 52 weeks, P < 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks, P < 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks, P = 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9-13.7 g/L vs. 4.8, range 1.5-12.3 g/L) decreased significantly, both P < 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed. Conclusion Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

“…In their study of 104 patients, Rahbar et al found that there was no incremental benefit to overall survival beyond a PSA decline of 21% [13]. However, Rasul et al noted that there was an added increase in survival, both progression-free and overall, with PSA declines of over 50% and over 80%, though they did not describe the extent [20]. In their prospective study, Hofman et al showed that patients with over 50% PSA decline had longer survival compared to patients with PSA decline of under 50% (17 months vs. 9.9 months) [14].…”

“…The salient features of reviewed studies are summarized in Table 1. With regard to predictors of response to therapy and overall survival, numerous studies have shown that patients with PSA decline in response to RLT experience longer overall survival compared to those who do not respond [12,[17][18][19][20][21][22][23][24][25]. It also appears that the degree of PSA decline correlates with the outcome.…”

“…Most have involved either six weeks or eight weeks. In a novel study, Rasul et al retrospectively examined 54 patients who received 7.3 GBq every four weeks for three cycles [20]. Response rates were high: 79.6% (43/54) with a PSA decline, 57.4% (31/54) with over 50% decline, and 35.2% (19/54) with over 80% PSA decline.…”

Improving quality of life in patients with metastatic prostate cancer following one cycle of 177Lu-PSMA-617 radioligand therapy: a pilot study

“…Interestingly, a PSA response of at least 50 % did explain only 9.6 % of respective variation. Following Prostate Cancer Clinical Trial Working Group criteria a PSA decrease surpassing (or equaling) 50 % has been defined in many studies as a biochemically relevant PSA response [2,17,[21][22][23][24], showing in fact a better overall survival [17,[21][22][23]. Against the backdrop of our findings it is important to critically discuss the clinical relevance of an at least 50 % PSA decrease, as its meaningfulness in terms of QoL is rather limited.…”

Obtenção de kit de PSMA-617 para pronta marcação com lutécio-177 e sua avaliação na aplicabilidade no tratamento do câncer de próstata

“…Este trabalho revelou que pacientes com maior expressão de PSMA tiveram uma sobrevida maior com relação aos que tinham as menores expressões.Contudo, ainda é incerto concluir se pacientes com baixa expressão de PSMA se beneficiam ou se são prejudicados com o uso de PSMA-617-177 Lu (SEIFERT et al, GBq de PSMA-617-177 Lu a cada 4 semanas reduziu o PSA em 79% dos pacientes, deste grupo 35% apresentaram redução superior a 80%. Após o terceiro ciclo, os principais efeitos adversos foram plaquetopenia e leucopenia.Os autores afirmaram que o aumento de sobrevida global de 119 semanas foi expressivo quando comparado com sobrevida média de 56 semanas nos estudos conduzidos com ciclos administrados a cada 8 semanas(RASUL et al, 2020).O PSMA-617 não tem sido apenas radiomarcado com lutécio-177 ou gálio-68, escândio-44 ou cobre-64 para avaliação in vitro e/ou in vivo. MBq).…”