Met dank aan Joge die me vroeg naar deze studie omdat een kennis van haar met in de botten uitgezaaide prostaatkanker na drie injecties met Lutetium-177 PSMA-617 klinisch kankervrij werd verklaard. En deze man kreeg zijn behandeling bij dr. Andre Bergman werkzaam in het Antoni van Leeuwenhoek ziekenhuis (AvL). Overigens ook in Utrecht in het UMC-MC worden prostaatkankerpatiënten behandeld met 177Lu-PSMA-617.
Al in 2021 werd een studie met 177Lu-PSMA-617 gepubliceerd (abstract staat verderop in dit artikel) en de FDA gaf toestemming tot gebruik in 2023, zie dit artikel.
Eind 2023 werd een fase III studie gepubliceerd bij patiënten die geen chemo hadden gehad maar wel uitgezaaide prostaatkanker, zie deze studie (abstract verderop).
Een aparte substudie naar de bijwerkingen op korte en lange termijn werd afgelopen jaar gepubliceerd, zie dit studiesverslag. (abstract verderop in dit artikel:
Je kunt je natuurlijk afvragen waarom wordt 177Lu-PSMA-617 niet in een veel vroeger stadium ingezet.
En waarom wordt 177Lu-PSMA-617 niet ingezet bij in de botten uitgezaaide borstkanker? Ik vind 1 studie bij 1 patiënt met uitgezaaide triple negatieve borstkanker, zie abstract verderop in dit artikel.
Samenvattend kun je zeggen dat 177Lu-PSMA-617 een veelbelovende behandeling is zonder ernstige bijwerkingen voor in de botten uitgezaaide prostaatkanker. In verschillende ziekenhuizen in Nederland wordt dus deze behandeling gegeven, zie eeerder in dit artikel.
Hier volgen de abstracten van genoemde studies:
Radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer.
Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
- PMID: 34161051
- PMCID: PMC8446332
- DOI: 10.1056/NEJMoa2107322
Abstract
Background: Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.
Methods: We conducted an international, open-label, phase 3 trial evaluating 177Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)-labeled PSMA-11 positron-emission tomographic-computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment.
Results: From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. 177Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval , 0.29 to 0.57; P<0.001) and overall survival (median, 15.3 vs. 11.3 months; hazard ratio for death, 0.62; 95% CI, 0.52 to 0.74; P<0.001). All the key secondary end points significantly favored 177Lu-PSMA-617. The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 than without (52.7% vs. 38.0%), but quality of life was not adversely affected.
Conclusions: Radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer. (Funded by Endocyte, a Novartis company; VISION ClinicalTrials.gov number, NCT03511664.).
Copyright © 2021 Massachusetts Medical Society.
Figures
177Lu-PSMA-617 prolonged rPFS vs ARPI change in taxane-naive pts with PSMA+ mCRPC, with a favourable safety profile.
PROSTATE CANCER| VOLUME 34, SUPPLEMENT 2, S1324-S1325, OCTOBER 2023
LBA13 Phase III trial of Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore)
Background
Methods
Results
Second OS IA (DCO, 21 Jun 2023; median follow-up, 15.9 months) | 177Lu-PSMA-617 (N=234) | ARPI change (N=234) |
---|---|---|
Cycles, median (range) | 6.0 (1–6) | – |
rPFSa | ||
Events, n (%) | 115 (49.1) | 168 (71.8) |
Median (95% CI), months | 12.02 (9.30, 14.42) | 5.59 (4.17, 5.95) |
HR (95% CI), p | 0.43 (0.33, 0.54), <0.0001 | |
TTW in FACT-P Totalb | ||
Events, n (%) | 167 (71.4) | 187 (79.9) |
Median (95% CI), months | 7.46 (6.08, 8.51) | 4.27 (3.48, 4.53) |
HR (95% CI) | 0.59 (0.47, 0.72) | |
N=105 | N=103 | |
ORRc, % (95% CI) | 41.9 (32.3, 51.9) | 12.6 (6.9, 20.6) |
N=44 | N=13 | |
DORc, median (95% CI), months | 17.1 (11.6, NE) | 10.1 (4.6, NE) |
Conclusions
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Funding
Disclosure
Article info
Identification
Copyright
ScienceDirect
Access this article on ScienceDirectHigher SUVmean is strongly associated with improved outcomes with 177Lu-PSMA-617; clinical efficacy for different SUV levels vs the SoC arm is being assessed. Data support use of 68Ga-PSMA-11 PET/CT scan to identify pts who will benefit from PSMA-targeted radioligand therapy.
[68Ga]Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [177Lu]Lu-PSMA-617 in patients with mCRPC: A VISION substudy.
Abstract
rPFSb | OSb | ORRc | PSA50c | |
---|---|---|---|---|
SUVmean | 0.86 [0.82, 0.90], < 0.001 |
0.88 [0.84, 0.91], < 0.001 |
1.43 [1.24, 1.65], < 0.001 |
1.34 [1.23, 1.45], < 0.001 |
SUVmax | NS | NS | 0.98 [0.96, 0.99], 0.009 | NS |
PSMA+ tumor volume | NS | NS | NS | NS |
Tumor load | 1.02 [1.01, 1.04], 0.001 | 1.04 [1.03, 1.05], < 0.001 |
NS | NS |
Absence of PSMA+ lesions in: | ||||
Bone | 0.45 [0.26, 0.78], 0.004 | 0.38 [0.22, 0.67], < 0.001 | 3.06 [1.12, 8.38], 0.03 | NS |
Liver | 0.48 [0.34, 0.67], < 0.001 | 0.49 [0.37, 0.66], < 0.001 | 2.55 [1.02, 6.34], 0.045 | 2.42 [1.21, 4.86], 0.013 |
Lymph node | NS | 0.74 [0.58, 0.94], 0.014 | 0.1 [0.04, 0.25], < 0.001 |
NS |
Soft tissue | NS | NS | NS | NS |
aPer unit increase for continuous variables. bHazard ratio [95% CI], p value; cOdds ratio [95% CI], p value. NS, not significant.
the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype.
Head-to-Head Comparison of [18F]PSMA-1007 and [18F]FDG PET/CT in Patients with Triple-Negative Breast Cancer
Associated Data
Abstract
Simple Summary
This study investigates a promising avenue for improving the diagnosis and treatment of triple-negative breast cancer (TNBC), a highly aggressive form of breast cancer with limited therapeutic options. The researchers focus on the prostate-specific membrane antigen (PSMA), known for its presence in prostate cancer but also identified in breast cancer. Using 18F-PSMA-1007 PET/CT, the study aims to assess PSMA’s in vivo expression in TNBC patients and compare it with the standard [18F]FDG PET/CT. The findings suggest that [18F]PSMA-1007 PET/CT may outperform current methods in detecting distant metastases, especially in the brain. This research not only enhances our understanding of PSMA expression in TNBC but also hints at potential advancements in diagnostic imaging and targeted therapies for this challenging cancer type.
Abstract
Background: Triple-negative breast cancer (TNBC) exhibits high aggressiveness and a notably poorer prognosis at advanced stages. Nuclear medicine offers new possibilities, not only for diagnosis but also potentially promising therapeutic strategies. This prospective study explores the potential of prostate-specific membrane antigen (PSMA) as a diagnostic and therapeutic target in TNBC. Methods: the research investigates PSMA expression in vivo among TNBC patients using [18F]PSMA-1007 PET/CT and compares it head-to-head with the standard-of-care [18F]FDG PET/CT. Results: The study involves 10 TNBC patients, revealing comparable uptake of [18F]PSMA-1007 and [18F]FDG in primary and metastatic lesions. Nodal metastases were found in eight patients, showing similar SUVmax values in both modalities. Two patients had uncountable lung metastases positive in both [18F]FDG and [18F]PSMA-1007 scans. PET-positive bone metastases were identified by 18F-PSMA in four patients, while elevated [18F]FDG uptake was found only in three of them. Distant metastases displayed higher SUVmax values in the [18F]PSMA-1007 PET/CT, as compared to [18F]FDG. Additionally, brain metastases were exclusively detected using [18F]PSMA-1007. Conclusions: the findings provide valuable insights into the expression of PSMA in TNBC and underscore the potential clinical significance of [18F]PSMA-1007 PET/CT in enhancing both diagnostic and therapeutic approaches for this aggressive breast cancer subtype
References studies with Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Comment in
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177Lu-PSMA-PET extends survival.Nat Rev Clin Oncol. 2021 Sep;18(9):542. doi: 10.1038/s41571-021-00543-8.PMID: 34262157 No abstract available.
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Re: Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.Eur Urol. 2021 Oct;80(4):520-521. doi: 10.1016/j.eururo.2021.07.006. Epub 2021 Jul 24.PMID: 34312019 No abstract available.
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177Lu-PSMA-PET extends survival.Nat Rev Urol. 2021 Sep;18(9):510. doi: 10.1038/s41585-021-00507-8.PMID: 34331044 No abstract available.
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Urological Oncology: Prostate Cancer.J Urol. 2022 Feb;207(2):467-469. doi: 10.1097/JU.0000000000002326. Epub 2021 Nov 17.PMID: 34784728 No abstract available.
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Radioligand Therapy for Metastatic Prostate Cancer.Radiol Imaging Cancer. 2021 Nov;3(6):e219026. doi: 10.1148/rycan.2021219026.PMID: 34825836 Free PMC article. No abstract available.
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Lutetium-177-PSMA-617 for Prostate Cancer.N Engl J Med. 2021 Dec 23;385(26):2494. doi: 10.1056/NEJMc2116647.PMID: 34936751 No abstract available.
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Lutetium-177-PSMA-617 for Prostate Cancer.N Engl J Med. 2021 Dec 23;385(26):2494-2495. doi: 10.1056/NEJMc2116647.PMID: 34936752 No abstract available.
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Lutetium-177-PSMA-617 for Prostate Cancer.N Engl J Med. 2021 Dec 23;385(26):2495. doi: 10.1056/NEJMc2116647.PMID: 34936753 No abstract available.
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Reply to Timothée Olivier, Kerrington Powell, Vinay Prasad. Lutetium-177-PSMA-617 in Metastatic Castration-resistant Prostate Cancer: Limitations of the VISION Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2022.08.022.Eur Urol. 2023 Jul;84(1):7-8. doi: 10.1016/j.eururo.2023.03.028. Epub 2023 Apr 7.PMID: 37032186 No abstract available.
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