Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&amp;T in Metastatic Castration-resistant Prostate Cancer

Heck, Matthias; Tauber, Robert; Schwaiger, Sebastian; Retz, Margitta; D’Alessandria, Calogero; Maurer, Tobias; Gafita, Andrei; Wester, Hans‐Jürgen; Gschwend, Jürgen E.; Weber, Wolfgang; Schwaiger, Markus; Knorr, Karina; Eiber, Matthias

doi:10.1016/j.eururo.2018.11.016

Cited by 224 publications

(266 citation statements)

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“…Rahbar et al 11 reported a PSA decline of ≥50% in 45% of patients in their retrospective multicenter study, and a PSA response in 40% of patients after one cycle. Using a different PSMA ligand, Heck et al 12 observed a PSA decline of ≥50% in 38% of patients receiving 177 Lu‐PSMA I&T. Hofman et al 10 reported higher overall response PSA rates of 57% of patients, however, their study cohort was considerably smaller. In this study, a PSA decline of 50% or more was achieved in 48% of patients, and 35% of patients already demonstrated a PSA response after the first cycle, underlining the high efficacy of 177 Lu‐PSMA‐617 in advanced mCRPC.…”

Section: Discussionmentioning

confidence: 98%

“…Small molecule inhibitors targeting the prostate‐specific membrane antigen, such as prostate‐specific membrane antigen (PSMA)‐617 or PSMA I&T, have recently gained increased interest for both imaging and therapy of prostate cancer 5‐9 . Both retrospective and prospective studies have reported favorable biochemical and imaging responses to 177 Lu‐labelled PSMA ligands 10‐15 . In a recent phase 2 study, Hofman et al 10 demonstrated that 177 Lu‐PSMA‐617 can induce a PSA decline of ≥50% in 57% of mCRPC patients, with limited toxic effects.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Demonstration of high uptake on 68 Ga‐PSMA‐PET is used for selection of patients for 177 Lu‐PSMA therapy. A number of retrospective studies with substantial variability in treatment regimens have demonstrated favourable PSA responses of >50% in 31–72% of heavily pre‐treated patients with mCRPC .…”

Section: Introductionmentioning

confidence: 99%

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

et al. 2019

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ObjectiveTo assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177 Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Results and Conclusions177 Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177 Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

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“…Additional prospective clinical trials are ongoing [e.g., TheraP (NCT03392428) and VISION (NCT03511664)] to evaluate the potential of this endoradiotherapy, especially with regard to improved patient survival. Another study including 100 patients treated with [ 177 Lu]Lu-PSMA-I&T showed that this tracer is also well-tolerated and demonstrated good treatment response in a subgroup of patients [176]. It was also observed that treatment outcome was worse in patients with organ metastases and elevated lactate dehydrogenase in blood tests.…”

Section: Prostate-specific Membrane Antigenmentioning

confidence: 99%

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Rangger

Haubner

2020

Pharmaceuticals

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This review deals with the development of peptide-based radiopharmaceuticals for the use with positron emission tomography and peptide receptor radiotherapy. It discusses the pros and cons of this class of radiopharmaceuticals as well as the different labelling strategies, and summarises approaches to optimise metabolic stability. Additionally, it presents different target structures and addresses corresponding tracers, which are already used in clinical routine or are being investigated in clinical trials.

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Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer

Cited by 224 publications

References 12 publications

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

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

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

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Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer

Cited by 224 publications

References 12 publications

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

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

TheraP: a randomized phase 2 trial of 177Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

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

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

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)