Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study

Bastiaan M. Privé; Steffie M.B. Peters; Constantijn H.J. Muselaers; Inge M. van Oort; Marcel J.R. Janssen; J. P. Michiel Sedelaar; Mark W. Konijnenberg; Patrik Zámecnik; Maike J.M. Uijen; Melline G.M. Schilham; Annemarie Eek; Tom W.J. Scheenen; J. Fred Verzijlbergen; Winald R. Gerritsen; Niven Mehra; Linda G.W. Kerkmeijer; Robert J. Smeenk; Diederik M. Somford; Jean Paul A. van Basten; Sandra Heskamp; Jelle O. Barentsz; Martin Gotthardt; J. Alfred Witjes; James Nagarajah

doi:10.1158/1078-0432.CCR-20-4298

Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study

Bastiaan M. Privé, Steffie M.B. Peters, Constantijn H.J. Muselaers, Inge M. van Oort, Marcel J.R. Janssen, J. P. Michiel Sedelaar, Mark W. Konijnenberg, Patrik Zámecnik, Maike J.M. Uijen, Melline G.M. Schilham, Annemarie Eek, Tom W.J. Scheenen, J. Fred Verzijlbergen, Winald R. Gerritsen, Niven Mehra, Linda G.W. Kerkmeijer, Robert J. Smeenk, Diederik M. Somford, Jean Paul A. van Basten, Sandra HeskampJelle O. Barentsz, Martin Gotthardt, J. Alfred Witjes, James Nagarajah^*

^*Corresponding author for this work

Radiology & Nuclear Medicine

Research output: Contribution to journal › Article › Academic › peer-review

73 Citations (Scopus)

Abstract

Purpose: [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (¹⁷⁷Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of ¹⁷⁷Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [⁶⁸Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of ¹⁷⁷Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of ¹⁷⁷Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: ¹⁷⁷Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.

Original language	English
Pages (from-to)	3595-3601
Number of pages	7
Journal	Clinical Cancer Research
Volume	27
Issue number	13
DOIs	https://doi.org/10.1158/1078-0432.CCR-20-4298
Publication status	Published - 1 Jul 2021

Bibliographical note

Funding Information:
B.M. Privéreports grants from Dutch Prostate Cancer Foundation and grants from Radboud Oncology Foundation during the conduct of the study. S.M.B. Peters reports grants from Radboud Oncologie Fonds and grants from Prostaatkanker-stichting during the conduct of the study. I.M. van Oort reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; I.M. van Oort also reports grants from Astellas, Janssen, Bayer, and MSD/AstraZeneca outside the submitted work. P. Zámecnik reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; P. Zámecnik is a scientific advisor to Saving Patients’ Lives Medical (SPL Medical) B.V., the Netherlands. M.J.M. Uijen reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study. A. Eek reports personal fees from Radboud Oncology Fund and personal fees from Dutch Prostate Cancer Foundation during the conduct of the

Publisher Copyright:
© 2021 American Association for Cancer Research.

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10.1158/1078-0432.CCR-20-4298

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Privé, B. M., Peters, S. M. B., Muselaers, C. H. J., van Oort, I. M., Janssen, M. J. R., Michiel Sedelaar, J. P., Konijnenberg, M. W., Zámecnik, P., Uijen, M. J. M., Schilham, M. G. M., Eek, A., Scheenen, T. W. J., Fred Verzijlbergen, J., Gerritsen, W. R., Mehra, N., Kerkmeijer, L. G. W., Smeenk, R. J., Somford, D. M., van Basten, J. P. A., ... Nagarajah, J. (2021). Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study. Clinical Cancer Research, 27(13), 3595-3601. https://doi.org/10.1158/1078-0432.CCR-20-4298

@article{eed062ecd0d749749b3f7dbac4c1b3f1,

title = "Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study",

abstract = "Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [68Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of 177Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: 177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.",

author = "Priv{\'e}, {Bastiaan M.} and Peters, {Steffie M.B.} and Muselaers, {Constantijn H.J.} and {van Oort}, {Inge M.} and Janssen, {Marcel J.R.} and {Michiel Sedelaar}, {J. P.} and Konijnenberg, {Mark W.} and Patrik Z{\'a}mecnik and Uijen, {Maike J.M.} and Schilham, {Melline G.M.} and Annemarie Eek and Scheenen, {Tom W.J.} and {Fred Verzijlbergen}, J. and Gerritsen, {Winald R.} and Niven Mehra and Kerkmeijer, {Linda G.W.} and Smeenk, {Robert J.} and Somford, {Diederik M.} and {van Basten}, {Jean Paul A.} and Sandra Heskamp and Barentsz, {Jelle O.} and Martin Gotthardt and {Alfred Witjes}, J. and James Nagarajah",

note = "Funding Information: B.M. Priv{\'e}reports grants from Dutch Prostate Cancer Foundation and grants from Radboud Oncology Foundation during the conduct of the study. S.M.B. Peters reports grants from Radboud Oncologie Fonds and grants from Prostaatkanker-stichting during the conduct of the study. I.M. van Oort reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; I.M. van Oort also reports grants from Astellas, Janssen, Bayer, and MSD/AstraZeneca outside the submitted work. P. Z{\'a}mecnik reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; P. Z{\'a}mecnik is a scientific advisor to Saving Patients{\textquoteright} Lives Medical (SPL Medical) B.V., the Netherlands. M.J.M. Uijen reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study. A. Eek reports personal fees from Radboud Oncology Fund and personal fees from Dutch Prostate Cancer Foundation during the conduct of the Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = jul,

day = "1",

doi = "10.1158/1078-0432.CCR-20-4298",

language = "English",

volume = "27",

pages = "3595--3601",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "13",

}

Privé, BM, Peters, SMB, Muselaers, CHJ, van Oort, IM, Janssen, MJR, Michiel Sedelaar, JP, Konijnenberg, MW, Zámecnik, P, Uijen, MJM, Schilham, MGM, Eek, A, Scheenen, TWJ, Fred Verzijlbergen, J, Gerritsen, WR, Mehra, N, Kerkmeijer, LGW, Smeenk, RJ, Somford, DM, van Basten, JPA, Heskamp, S, Barentsz, JO, Gotthardt, M, Alfred Witjes, J & Nagarajah, J 2021, 'Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study', Clinical Cancer Research, vol. 27, no. 13, pp. 3595-3601. https://doi.org/10.1158/1078-0432.CCR-20-4298

TY - JOUR

T1 - Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer

T2 - A prospective pilot study

AU - Privé, Bastiaan M.

AU - Peters, Steffie M.B.

AU - Muselaers, Constantijn H.J.

AU - van Oort, Inge M.

AU - Janssen, Marcel J.R.

AU - Michiel Sedelaar, J. P.

AU - Konijnenberg, Mark W.

AU - Zámecnik, Patrik

AU - Uijen, Maike J.M.

AU - Schilham, Melline G.M.

AU - Eek, Annemarie

AU - Scheenen, Tom W.J.

AU - Fred Verzijlbergen, J.

AU - Gerritsen, Winald R.

AU - Mehra, Niven

AU - Kerkmeijer, Linda G.W.

AU - Smeenk, Robert J.

AU - Somford, Diederik M.

AU - van Basten, Jean Paul A.

AU - Heskamp, Sandra

AU - Barentsz, Jelle O.

AU - Gotthardt, Martin

AU - Alfred Witjes, J.

AU - Nagarajah, James

N1 - Funding Information: B.M. Privéreports grants from Dutch Prostate Cancer Foundation and grants from Radboud Oncology Foundation during the conduct of the study. S.M.B. Peters reports grants from Radboud Oncologie Fonds and grants from Prostaatkanker-stichting during the conduct of the study. I.M. van Oort reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; I.M. van Oort also reports grants from Astellas, Janssen, Bayer, and MSD/AstraZeneca outside the submitted work. P. Zámecnik reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study; P. Zámecnik is a scientific advisor to Saving Patients’ Lives Medical (SPL Medical) B.V., the Netherlands. M.J.M. Uijen reports grants from Radboud Oncologie Fonds and grants from Prostaatkankerstichting during the conduct of the study. A. Eek reports personal fees from Radboud Oncology Fund and personal fees from Dutch Prostate Cancer Foundation during the conduct of the Publisher Copyright: © 2021 American Association for Cancer Research.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [68Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of 177Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: 177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.

AB - Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [68Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of 177Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: 177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.

UR - http://www.scopus.com/inward/record.url?scp=85109186645&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-20-4298

DO - 10.1158/1078-0432.CCR-20-4298

M3 - Article

C2 - 33883176

AN - SCOPUS:85109186645

SN - 1078-0432

VL - 27

SP - 3595

EP - 3601

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 13

ER -

Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study

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