Influence of short‐term dexamethasone on the efficacy of ¹⁷⁷Lu‐PSMA‐617 in patients with metastatic castration‐resistant prostate cancer

Abstract

Background and Aim: Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with 177 Lu-prostate-specific membrane antigen (PSMA)-617.Patients and Methods: Seventy-one patients with mCRPC were treated with 1 to 5 cycles of 177 Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT.Results: PSA response rates were not significantly different between patients receiving 177 Lu-PSMA-617 plus dexamethasone and those receiving 177 Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (−21% ± 50% vs +11% ± 90%, P = .08; −21% ± 69% vs +22% ± 116%, P = .07; −13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving 177 Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20).Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases. ---This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. contributed equally. Conclusions:We observed high response rates to 177 Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to 177 Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting. K E Y W O R D S glucocorticoids, prostate-specific membrane antigen (PSMA), PSMA-617, steroids, therapy 2.2 | GMP-compliant preparation of the PSMA-targeting ligand 177 Lu-PSMA-617 Lutetium-177 was purchased from Isotope Technologies Garching GmbH (Germany) as GMP-certified 177 Lu-LuCl 3 in 0.04M HCl-solution (EndolucinBeta, 40 GBq/mL) in no carrier added (n.c.a.) quality. 620 | DERLIN ET AL.

Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review

“…Gafita et al [37] found no association between PSA level and either PFS or OS, in a cohort with the median PSA baseline of 126 ng/ml (IQR: 37-368). Moreover, Derlin et al [38] found no [39] or any PSA response [40]. In summary, the prognostic value of baseline PSA level has been controversially discussed, which warrants further investigations.…”

“…Also, the same research group reported that a baseline LDH level of < 248 mg/L and any change after the first cycle could predict better survival [32]. However, others did not find a correlation between higher LDH and response to therapy or OS [24,38,39,63]. Moreover, some authors showed that abnormal pre-treatment LDH has no prognostic value for predicting OS [23,33,36].…”

“…Furthermore, according to the simple linear regression analysis by Derlin et al [38], it has been demonstrated that previous treatments, including abiraterone, enzalutamide, chemotherapy, and external radiation therapy, do not have a significant association with change in PSA following [ 177 Lu]Lu-PSMA RLT. The use of abiraterone, steroid, or previous radiotherapy, as depicted by Suman et al [48], did not stand as predictors of PFS or OS following [ 177 Lu]Lu-PSMA RLT.…”

“…Also, the absence of visceral metastasis predicted longer PSA PFS (HR: 0.51) [37]. Contrarily, Ferdinandus et al [24] and Derlin et al [38] reported that liver metastasis does not influence the PSA response. Additionally, no correlation was demonstrated between visceral metastasis and PSA response [55] or OS [23,30,39], in other studies.…”

“…They have a better outcome than those with metastasis in other organs [58]. Multiple studies have reported that the presence of lymph node metastasis does not impact the outcome (including PSA response or survival) after [ 177 Lu]Lu-PSMA RLT [4,24,28,30,38,39,50,55]. Noteworthy, the studies rarely have evaluated the patients with lymph node-only metastasis [50].…”