1392P Lutetium-177-prostate-specific membrane antigen therapy (177Lu-PSMA) in patients (Pts) with prior radium-223 (223Ra): Safety and effectiveness outcomes

Rahbar, Kambiz; Essler, Markus; Eiber, M.; Fougère, C. la; Prasad, Vikas; Fendler, WP; Rassek, P.; Hasa, Ergela; Dittmann, H.; Bundschuh, Ralph A.; Pabst, Kim M.; Kurtinecz, Milena; Schmall, Anja; Verholen, Frank

doi:10.1016/j.annonc.2022.07.1524

Cited by 5 publications

(3 citation statements)

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“…In addition, the current regulatory requirement for prior chemotherapy treatment is problematic as it has been demonstrated in population-based studies that the majority of patients with mCRPC within Canada never receive taxane chemotherapy during their disease course due to comorbidities that are common in this patient population, which is generally of advanced age [40]. Moreover, while patients who had been treated with radium-223 within six months were excluded from the VISION trial, real-world data suggest that treatment with radium-223 is feasible both before and after 177 Lu-PSMA-617 [41,42]. Other sequencing issues that have yet to be clarified include the benefits of RLT vs. docetaxel and its place in chemotherapy-naïve patients.…”

Section: Treatment Sequencing and Patient Selection Criteriamentioning

confidence: 99%

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

Chi,

Yip,

Bauman

et al. 2024

Current Oncology

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Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

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Section: Treatment Sequencing and Patient Selection Criteriamentioning

confidence: 99%

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

Chi,

Yip,

Bauman

et al. 2024

Current Oncology

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“…The RALU study demonstrated that 177 Lu-PSMA therapy in patients previously treated with radium-223 (Ra223) had an acceptable safety profile and effectiveness in terms of OS and rPFS, and was similar to other findings with 177 Lu-PSMA, indicating no cross-resistance. 23 Therefore, patients who have received Ra223 are still good candidates for 177 Lu-PSMA.…”

Section: E591mentioning

confidence: 99%

2022 European Society for Medical Oncology: Meeting highlights

Rendon

Hotte

Morgan

et al. 2022

CUAJ

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“…Grade 3-4 anemia necessitating a blood transfusion was seen in 5 patients, 2 patients required a dose-reduction and 7 patients discontinued treatment due to significant cytopaenias. Following this analysis, the authors concluded that treatment with [ 177 prior data and found that sequential therapy was feasible and well-tolerated (21).…”

Section: Introductionmentioning

confidence: 99%

AlphaBet: Combination of Radium-223 and [177Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol)

et al. 2022

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Background[177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 μm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses.MethodsThis is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&T, concurrently with 223Ra in escalating doses (28 kBq/kg – 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&T and the 50% PSA response rate.ConclusionThe AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months.Study registrationNCT05383079.

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1392P Lutetium-177-prostate-specific membrane antigen therapy (177Lu-PSMA) in patients (Pts) with prior radium-223 (223Ra): Safety and effectiveness outcomes

Cited by 5 publications

References 0 publications

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

2022 European Society for Medical Oncology: Meeting highlights

AlphaBet: Combination of Radium-223 and [177Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol)

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