Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy

Doelen, Maarten J. van der; Mehra, Niven; Oort, Inge M. van; Looijen-Salamon, Monika; Janssen, Marcel J.R.; Custers, José A. E.; Slootbeek, Peter H. J.; Kroeze, Leonie I.; Bruchertseifer, Frank; Morgenstern, Alfred; Haberkorn, Uwe; Kratochwil, Clemens; Nagarajah, James; Gerritsen, Winald R.

doi:10.1016/j.urolonc.2020.12.002

Cited by 46 publications

(63 citation statements)

References 32 publications

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“…The patients reported outcome assessed by the EORTC-QLQ-30 and BM-22 questionnaires showed a significant decrease in pain complain and a corresponding decrease in the need for analgesics. There was a progressively increase in the scores for physical and role functioning scales from after therapy completion [79]. Put together, these three studies show a consistent improvement in the quality of life of patients with mCRPC who were treated with 225 Ac-PSMA-617.…”

Section: Current Evidence For the Efficacy Of 225 Ac-psma Therapy In Mcrpcmentioning

confidence: 56%

“…The physical symptoms that showed improvement with 225 Ac-PSMA-617 therapy were pain, difficulty with urination, fatigue, and restriction in physical activity [78]. The positive impact of 225 Ac-PSMA-617 on patients' quality of life was also demonstrated in a report from Nijmegen, the Netherlands, of Dutch patients treated at Heidelberg, Germany, with 225 Ac-PSMA-617 for mCRPC [79]. The patients reported outcome assessed by the EORTC-QLQ-30 and BM-22 questionnaires showed a significant decrease in pain complain and a corresponding decrease in the need for analgesics.…”

Section: Current Evidence For the Efficacy Of 225 Ac-psma Therapy In Mcrpcmentioning

confidence: 99%

“…The most used phenotypical characteristic to select patients for PRLT is the level of PSMA expression. Low PSMA expression corresponds to a high tumor proliferative index and poor survival after 225 Ac-PSMA TAT [79]. Therapy-induced neuroendocrine differentiation is another histologically determined phenotype that portends poor treatment outcomes [79].…”

Section: Resistance and Mutationmentioning

confidence: 99%

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Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge

Bruchertseifer

Vorster

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose This review discusses the current state of prostate-specific membrane antigen (PSMA)-based alpha therapy of metastatic castration-resistant prostate cancer (mCRPC). With this in-depth discussion on the growing field of PSMA-based alpha therapy (PAT), we aimed to increase the interactions between basic scientists and physician–scientists in order to advance the field. Methods To achieve this, we discuss the potential, current status, and opportunities for alpha therapy and strategies, attempted to date, and important questions that need to be addressed. The paper reviews important concepts, including whom to treat, how to treat, what to expect regarding treatment outcome, and toxicity, and areas requiring further investigations. Results There is much excitement about the potential of this field. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other conventional therapies. Conclusion A better understanding of the strengths and limitations of PAT may help in creating an effective therapy for mCRPC and design a rational combinatorial approach to treatment by targeting different tumor pathways.

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Section: Current Evidence For the Efficacy Of 225 Ac-psma Therapy In Mcrpcmentioning

confidence: 56%

Section: Current Evidence For the Efficacy Of 225 Ac-psma Therapy In Mcrpcmentioning

confidence: 99%

Section: Resistance and Mutationmentioning

confidence: 99%

See 1 more Smart Citation

Global experience with PSMA-based alpha therapy in prostate cancer

Sathekge

Bruchertseifer

Vorster

et al. 2021

Eur J Nucl Med Mol Imaging

Self Cite

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“…The question of whether PSMA overexpression in mCRPC patients undergoing treatment with PSMA-TRT could represent a prognostic or predictive tool has yet to be fully elucidated. In a small cohort of 13 patients who received targeted alpha radiation therapy with 225 Ac-labeled PSMA ligands, those with high baseline immunohistochemical PSMA expression H-score of ≥200, defined semiquantitatively on a scale of 0−300 as a composite of the percentage of immunopositive tumor cells (0−100%) and the staining intensity (0 = negative; 1+ = weak; 2+ = moderate; 3+ = intense), tended to have longer OS compared to those with H-score < 200 (12.8 vs. 1.8 months, respectively) [ 50 ].…”

Section: Molecular Biomarkersmentioning

confidence: 99%

“…The presence of pathogenic BRCA1 mutations was associated with longer OS (16.1 vs. 7.6 months) after treatment with 25 Ac-PSMA-617 [ 50 ]. Anecdotal response of ATM mutation-positive mCRPC to beta-radiation with 177 Lu-PSMA-617 and concomitant enzalutamide is in line with a potential role of DDR defects in sensitizing to PSMA-TRT [ 54 ].…”

Section: Molecular Biomarkersmentioning

confidence: 99%

Biomarkers in Prostate-Specific Membrane Antigen Theranostics

2021

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Theranostics of prostate cancer (PC) represents a growing area of development of imaging agents and targeted radionuclide therapeutics against a major target, prostate specific membrane antigen (PSMA). In view of the encouraging efficacy from the use of 177Lu and other radionuclides in metastatic castration-resistant prostate cancer (mCRPC), it is becoming increasingly important to identify surrogate markers that can help predict which patients are more likely to respond and experience improved survival. This review discusses potential predictors of efficacy of PSMA-targeted radionuclide therapies (TRT) segregated in three major categories: imaging, clinical and molecular.

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Clinical Pharmacology of Radiotheranostics in Oncology

Beek

Burggraaf

Teunissen

et al. 2022

Clin Pharma and Therapeutics

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The combined use of diagnostic and therapeutic radioligands with the same molecular target, also known as theranostics, enables accurate patient selection, targeted therapy, and prediction of treatment response. Radioiodine, bone‐seeking radioligands and norepinephrine analogs have been used for many years for diagnostic imaging and radioligand therapy of thyroid carcinoma, bone metastases, pheochromocytoma, paraganglioma, and neuroblastoma, respectively. In recent years, radiolabeled somatostatin analogs and prostate‐specific membrane antigen ligands have shown clinical efficacy in the treatment of neuroendocrine tumors and prostate cancer, respectively. Several candidate compounds are targeting novel theranostic targets such as fibroblast activation protein, C‐X‐C chemokine receptor 4, and gastrin‐releasing peptide receptor. In addition, several strategies to improve efficacy of radioligand therapy are being evaluated, including dosimetry‐based dose optimization, multireceptor targeting, upregulation of target receptors, radiosensitization, pharmacogenomics, and radiation genomics. Design and evaluation of novel radioligands and optimization of dose and dose schedules, within the complex context of individualized multimodal cancer treatment, requires a multidisciplinary approach that includes clinical pharmacology. Significant increases in the use of these radiopharmaceuticals in routine oncological practice can be expected, which will have major impact on patient care as well as (radio)pharmacy utilization.

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Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy

Cited by 46 publications

References 32 publications

Global experience with PSMA-based alpha therapy in prostate cancer

Global experience with PSMA-based alpha therapy in prostate cancer

Biomarkers in Prostate-Specific Membrane Antigen Theranostics

Clinical Pharmacology of Radiotheranostics in Oncology

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