Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer

Rahbar, Kambiz; Bode, Axel; Weckesser, Matthias; Avramović, Nemanja; Claesener, Michael; Stegger, Lars; Bögemann, Martin

doi:10.1097/rlu.0000000000001240

Cited by 165 publications

(129 citation statements)

References 23 publications

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“…In the present study, only 4% of the patients experienced a grade $ 3 thrombocytopenia. Favorable safety of 177 Lu-PSMA-617 was previously reported in smaller patient cohorts (13)(14)(15)(16) and is now confirmed in this large multicenter dataset. The adverse events may be due to the advanced disease and prior toxic therapies and in part related to the performed RLT.…”

Section: Discussionsupporting

confidence: 80%

“…Detailed radiosynthesis procedures have been described in detail before (12,(14)(15)(16). Quality control parameters were monitored by experienced radiochemists and double checked by attending physician as follows: radiochemical purity, radiochemical identity, pH value, ethanol content, endotoxin content, and proof of sterility.…”

Section: Patient Populationmentioning

confidence: 99%

“…Since 2015, several studies reported promising results for response rates and a favorable safety profile after radioligand therapy (RLT) with 177 Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) (12)(13)(14)(15)(16). In a single-center study of 28 patients, a slight improvement of survival compared with a matched group of best supportive-care patients (historical population) was demonstrated (16). However, each group presented insight only into a small patient cohort, with insufficient power for the evaluation of a new therapy.…”

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confidence: 99%

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German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

et al. 2016

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177 Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castrationresistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177 Lu-PSMA-617 in a large cohort of patients. Methods: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177 Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline $ 50% from baseline to at least 2 wk after the start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177 Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

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Section: Discussionsupporting

confidence: 80%

Section: Patient Populationmentioning

confidence: 99%

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German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

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“…The small molecule PSMA-617 was demonstrated by recent studies to be safe for PRLT and to have a low toxicity profile, in line with our own experience (24)(25)(26).…”

Section: The Bad Berka Experiencesupporting

confidence: 80%

PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013

et al. 2016

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A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with 68 Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with 177 Lu-PSMA ligands. 68 Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring. Our comprehensive experience over the last 3 years using different radioligands indicates that PRLT is highly effective for the treatment of mCRPC, even in advanced cases, and potentially lends a significant benefit to overall and progression-free survival. Additionally, significant improvement in clinical symptoms and excellent palliation of pain can be achieved.

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“…Simultaneously, the PSA response rates are lower in comparison to the older 131 I-PSMA-RLT data exploiting the full 1 Gy red-marrow tolerance limit (10,16). Surprisingly, none of the authors (22)(23)(24)(25)(26)(27)(28) discussed the possibility that escalation of 177 Lu treatment activity to an estimated redmarrow absorbed dose between 0.2-1.0 Gy should still be well tolerable but offers the chance to further improve anti-tumor-activity because a positive dose/responserelationship is normally expected in radiotherapy. Therefore, after clinical introduction of 177 Lu-PSMA-617, for us it seemed ethical mandatory to increase treatment activity until either non-dramatically grade-1/2 toxicities appear or patients achieve enduring remissions.…”

Section: Responsementioning

confidence: 99%

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

et al. 2017

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Current treatment protocols for 177Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically.We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol 177 Lu-activity / precursor-amount (n=10, respectively) every 2 months. Safety lab was checked every 2 weeks, PSA-response every 4 weeks; other effects were assessed per anamnesis. Results: Initial PSA response presented no correlation to treatment activity. However, 2/10, 4/10, 4/10 and 7/10 patients with doses of 4, 6, 7.4 and 9.3 GBq were in partial remission 8 weeks after completing all 3 cycles;This would be in line with, but due to low patient numbers not proving, a positive doseresponse-relationship. Acute hematological toxicity was also irrespective of treatment activity and no more than one grade-3/4 toxicity was observed in each group.Nevertheless, in contrast to the other groups the mean platelet count in the 9. (8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13). Thus, dosimetry in nuclear medicine can only approximate a guidance level for dosing RLT but the optimal treatment regime has still to be refined clinically.In this retrospective analysis we report our clinical experience with fractions of 4 GBq, 6GBq, 7.4 GBq or 9.3 GBq 177 Lu-PSMA-617 repeated every 2 months.by on May 10, 2018. For personal use only. jnm.snmjournals.org Downloaded from MATERIALS AND METHODS Patients 177Lu-PSMA-RLT was performed under the conditions of the updated declaration of Helsinki, § 37 (Unproven interventions in clinical practice) and in accordance to the German Pharmaceuticals Law §13(2b) as a salvage therapy for patients with mCRPC, which had to be resistant against or ineligible for approved options and presented with progressive disease. Patient selection is outlined in Fig. 1. For patients stratified to 177 Lu-PSMA-617, each dose level was administered to 10 consecutive patients. If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig. 2. Patient characteristics were summarized in (Table 1). All patients were informed about the experime...

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Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer

Abstract: Results from 50 therapies show that radioligand therapy with Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.

Cited by 165 publications

References 23 publications

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

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Radioligand Therapy With 177Lu-PSMA-617 as A Novel Therapeutic Option in Patients With Metastatic Castration Resistant Prostate Cancer

Abstract: Results from 50 therapies show that radioligand therapy with Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.

Cited by 165 publications

References 23 publications

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013

Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

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German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

German Multicenter Study Investigating¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq