Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review

Heidegger, Isabel; Kesch, Claudia; Kretschmer, Alexander; Tsaur, Igor; Ceci, Francesco; Valério, Massimo; Tilki, Derya; Marra, Giancarlo; Preißer, Felix; Fankhauser, Christian Daniel; Zattoni, Fabio; Chiu, Peter Ka Fung; Puche-Sanz, Ignacio; Olivier, Jonathan; Bergh, Roderik C. N. van den; Kasivisvanathan, Veeru; Pircher, Andreas; Virgolini, Irene; Gandaglia, Giorgio

doi:10.1177/17588359221081922

Cited by 14 publications

(7 citation statements)

References 56 publications

(122 reference statements)

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“…The clinical results of this translational study are consistent with the dozens of published clinical studies on the efficacy and toxicity of various 177 Lu-labeled ligands for the treatment of advanced and progressive mCRPC and GEP-NET [7,8,[16][17][18].…”

Section: Discussionsupporting

confidence: 84%

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses

et al. 2023

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177Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177Lu-iPSMA and 177Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177Lu-iPSMA and 177Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177Lu-iPSMA (range 1–5 administrations; 394 treatment doses) or 177Lu-DOTATOC (range 2–8 administrations; 511 treatment doses) at intervals of 1.5–2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10–7 to 3–1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177Lu-iPSMA and 177Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

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Section: Discussionsupporting

confidence: 84%

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses

et al. 2023

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“…Many predictive biomarkers based on laboratory and imaging findings are being investigated. 41 , 42 In a multicenter retrospective study, Gafita and colleagues developed nomograms to predict OS, PSA PFS, and PSA50 (PSA decline of at least 50% from baseline). 43 The authors took data from two prior phase II clinical trials (NCT03042312 and ACTRN12615000912583) and compassionate use at participating sites with patients who had received either 6.0–8.5 GBq of 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T every 6–8 weeks for a maximum of six cycles.…”

Section: Predicting Outcomes With Psma-rltmentioning

confidence: 99%

Status of PSMA-targeted radioligand therapy in prostate cancer: current data and future trials

Jang

Kendi

2023

Ther Adv Med Oncol

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Metastatic prostate cancer continues to be an incurable disease. Despite all the novel therapies approved in the past two decades, overall patient outcomes remain relatively poor, and these patients die on a regular basis. Clearly, improvements in current therapies are needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer given its increased expression on the surface of the prostate cancer cells. PSMA small molecule binders include PSMA-617 and PSMA-I&T and monoclonal antibodies such as J591. These agents have been linked to different radionuclides including beta-emitters such as lutetium-177 and alpha-emitters such as actinium-225. The only regulatory-approved PSMA-targeted radioligand therapy (PSMA-RLT) to date is lutetium-177–PSMA-617 in the setting of PSMA-positive metastatic castration-resistant prostate cancer that has failed androgen receptor pathway inhibitors and taxane chemotherapy. This approval was based on the phase III VISION trial. Many other clinical trials are evaluating PSMA-RLT in various settings. Both monotherapy and combination studies are underway. This article summarizes pertinent data from recent studies and provides an overview of human clinical trials in progress. The field of PSMA-RLT is rapidly evolving, and this therapeutic approach will likely play an increasingly important role in the years to come.

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“…54 On the same topic, several studies report that PSMA total tumor volume is associated with OS and/or PSA response during 177 Lu-PSMA-617 therapy while tumor-to-liver ratio independently can predict PFS of this treatment modality. 55…”

Section: Psma Radionuclide Therapymentioning

confidence: 99%

Current role of PSMA-PET imaging in the clinical management of prostate cancer

Georgakopoulos,

Bamias,

Chatziioannou

2023

Ther Adv Med Oncol

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Despite the developments of the last few years, metastatic castration-resistant prostate cancer (PC) remains a deadly disease. Until recently, almost all guidelines recommended magnetic resonance imaging (MRI) or computed tomography (CT) for the initial staging and local/systematic recurrence. Positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) at the present stage, emerged as a promising diagnostic imaging tool for PC. PSMA PET/CT alone or in combination with multiparametric magnetic resonance imaging (mpMRI) can improve the detection of clinically significant PC, especially for Prostate Imaging Reporting & Data System (PI-RADS) = 3 lesions. In addition, PSMA PET/CT is more accurate than CT and bone scan for intermediate to high-risk disease at the initial staging. Contrariwise, a negative PET is not useful for surgeons to avoid a pelvic nodal dissection. PET-PSMA imaging is appropriate for prostate-specific antigen (PSA) persistence or PSA rise from undetectable level after radical prostatectomy or for PSA rise above nadir after definitive radiotherapy. Also, it is recommended for patients fit for curative salvage treatment. It should be noted that in patients, candidates for radionuclide therapy with Lutetium-177 (117Lu), a PSMA strong expression from PET/CT at baseline is considered necessary. This review summarizes the evolution of PSMA PET/CT and its current role in the management of PC.

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Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review

Cited by 14 publications

References 56 publications

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses

Status of PSMA-targeted radioligand therapy in prostate cancer: current data and future trials

Current role of PSMA-PET imaging in the clinical management of prostate cancer

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