The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Michael S Hofman - One of the best experts on this subject based on the ideXlab platform.
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Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies
Prostate Cancer and Prostatic Diseases, 2020Co-Authors: Amir Iravani, John Violet, Arun Azad, Michael S HofmanAbstract:Theranostic principles utilize a molecular biomarker specific for a tumor target, initially for imaging to assess target expression and, if deemed suitable, for targeted therapy. This presents an exciting opportunity for a highly personalized treatment strategy in the era of precision medicine. Prostate-specific membrane antigen (PSMA) theranostics has attracted increasing attention as a promising targeted treatment in metastatic prostate cancer (PC). ^177Lu-DOTA-PSMA-617 (^177Lu-PSMA-617) is a PSMA-targeted small molecule with favorable properties and is the most extensively investigated PSMA radioligand for radionuclide therapy (RNT) in PC. Since 2014 multiple retrospective studies and more recently a phase II prospective study demonstrated safety and impressive efficacy of ^177Lu-PSMA RNT. The evidence generated by these trials led to two currently underway randomized trials in metastatic castrate-resistant PC: TheraP (NCT03392428) and VISION (NCT03511664). While we wait for these pivotal trials to read out, nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists are facing a steep learning curve to master the intricacies and nuances of this novel therapeutic strategy. This review article aims to share and discuss the evolving experience in practical aspects of PSMA theranostics.
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results of a 50 patient single center phase ii prospective trial of Lutetium 177 psma 617 theranostics in metastatic castrate resistant prostate cancer
Journal of Clinical Oncology, 2019Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Rodney J Hicks, Jennifer MooiAbstract:228Background: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling targeted delivery of beta...
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high activity pain reduction and low toxicity with Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc results of a phase ii prospective trial
The Journal of Nuclear Medicine, 2018Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Shahneen Sandhu, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Price JacksonAbstract:531 Background: Retrospective studies demonstrate high response rates of Lutetium-177 (177Lu)-PSMA617 (LuPSMA), a radiolabelled small molecule, that binds with high affinity to prostate specific membrane antigen (PSMA) in men with mCRPC. Methods. In this phase II prospective trial, 30 pts with PSMA-avid mCRPC who had failed standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Patients were included if they had high uptake on 68Ga-PSMA PET/CT defined by tumor SUVmax greater than 1.5 times liver and were excluded if FDG PET/CT demonstrated sites of PSMA-negative disease. Administered activity (6 GBq ± 2 GBq) was adjusted according to tumor burden ( 20 sites), renal function (GFR 90 mL/min) and weight ( 90 Kg). The primary endpoints were PSA response (PCWG2) and toxicity (CTCAE v4). Other endpoints were imaging response (PCWG2 RECIST), quality of life (EORTC QLQ-C30, BPI), dosimetry, PFS and OS. Australian New Zealand Clinical Trials Registry, ACTRN12615000912583. Results. 47 men were screened to identify 30 patients eligible for treatment. 83% progressed after abiraterone and/or enzalutamide, and 87% progressed after chemotherapy including 47% following cabazitaxel. The mean administered activity was 7.5 GBq/cycle. The primary endpoint of PSA decline ≥ 50% was achieved in 17 of 30 patients (57%, 95% CI 37-75%), including 11 patients (37%, 95% CI 20-56%) with a PSA decline ≥ 80%. The most common toxicity was dry mouth in 87% of patients, all grade 1 in severity. Grade 3 or greater thrombocytopenia possibly attributed to LuPSMA occurred in 13% of patients. An objective imaging response was seen in 82% of the subgroup of 17 patients who had evaluable soft tissue disease. The overwhelming pattern of progression was seen in non-target marrow disease. Pain severity and interference scores improved significantly at all time points. Median PSA progression free survival was 7·6 months (95% CI 6·4-9·0) and median OS was 13·5 months (95% CI 10·4-22·7). Conclusions. This LuPSMA Phase II trial provides evidence of high response rates, pain reduction and low toxicity in men with mCRPC who progressed after conventional therapies. These compelling results indicate the need for randomised trials comparing LuPSMA to existing standard-of-care.
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prostate specific membrane antigen theranostics therapy with Lutetium 177
Current Opinion in Urology, 2017Co-Authors: Justin Ferdinandus, John Violet, Shahneen Sandhu, Michael S HofmanAbstract:Purpose of reviewProstate-specific membrane antigen (PSMA) theranostics offers a new approach for a personalized and targeted treatment for metastatic prostate cancer. Lutetium-177-labelled PSMA-ligands (177Lu-PSMA) is a radionuclide therapy that is directed to PSMA expressing prostate cancer. Clini
John Violet - One of the best experts on this subject based on the ideXlab platform.
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Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies
Prostate Cancer and Prostatic Diseases, 2020Co-Authors: Amir Iravani, John Violet, Arun Azad, Michael S HofmanAbstract:Theranostic principles utilize a molecular biomarker specific for a tumor target, initially for imaging to assess target expression and, if deemed suitable, for targeted therapy. This presents an exciting opportunity for a highly personalized treatment strategy in the era of precision medicine. Prostate-specific membrane antigen (PSMA) theranostics has attracted increasing attention as a promising targeted treatment in metastatic prostate cancer (PC). ^177Lu-DOTA-PSMA-617 (^177Lu-PSMA-617) is a PSMA-targeted small molecule with favorable properties and is the most extensively investigated PSMA radioligand for radionuclide therapy (RNT) in PC. Since 2014 multiple retrospective studies and more recently a phase II prospective study demonstrated safety and impressive efficacy of ^177Lu-PSMA RNT. The evidence generated by these trials led to two currently underway randomized trials in metastatic castrate-resistant PC: TheraP (NCT03392428) and VISION (NCT03511664). While we wait for these pivotal trials to read out, nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists are facing a steep learning curve to master the intricacies and nuances of this novel therapeutic strategy. This review article aims to share and discuss the evolving experience in practical aspects of PSMA theranostics.
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results of a 50 patient single center phase ii prospective trial of Lutetium 177 psma 617 theranostics in metastatic castrate resistant prostate cancer
Journal of Clinical Oncology, 2019Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Rodney J Hicks, Jennifer MooiAbstract:228Background: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling targeted delivery of beta...
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Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc interim results of a phase ii trial
Journal of Clinical Oncology, 2018Co-Authors: Shahneen Sandhu, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Christina Guo, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Alexis BeaulieuAbstract:5040Background: Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling tumor-targeted delivery o...
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high activity pain reduction and low toxicity with Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc results of a phase ii prospective trial
The Journal of Nuclear Medicine, 2018Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Shahneen Sandhu, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Price JacksonAbstract:531 Background: Retrospective studies demonstrate high response rates of Lutetium-177 (177Lu)-PSMA617 (LuPSMA), a radiolabelled small molecule, that binds with high affinity to prostate specific membrane antigen (PSMA) in men with mCRPC. Methods. In this phase II prospective trial, 30 pts with PSMA-avid mCRPC who had failed standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Patients were included if they had high uptake on 68Ga-PSMA PET/CT defined by tumor SUVmax greater than 1.5 times liver and were excluded if FDG PET/CT demonstrated sites of PSMA-negative disease. Administered activity (6 GBq ± 2 GBq) was adjusted according to tumor burden ( 20 sites), renal function (GFR 90 mL/min) and weight ( 90 Kg). The primary endpoints were PSA response (PCWG2) and toxicity (CTCAE v4). Other endpoints were imaging response (PCWG2 RECIST), quality of life (EORTC QLQ-C30, BPI), dosimetry, PFS and OS. Australian New Zealand Clinical Trials Registry, ACTRN12615000912583. Results. 47 men were screened to identify 30 patients eligible for treatment. 83% progressed after abiraterone and/or enzalutamide, and 87% progressed after chemotherapy including 47% following cabazitaxel. The mean administered activity was 7.5 GBq/cycle. The primary endpoint of PSA decline ≥ 50% was achieved in 17 of 30 patients (57%, 95% CI 37-75%), including 11 patients (37%, 95% CI 20-56%) with a PSA decline ≥ 80%. The most common toxicity was dry mouth in 87% of patients, all grade 1 in severity. Grade 3 or greater thrombocytopenia possibly attributed to LuPSMA occurred in 13% of patients. An objective imaging response was seen in 82% of the subgroup of 17 patients who had evaluable soft tissue disease. The overwhelming pattern of progression was seen in non-target marrow disease. Pain severity and interference scores improved significantly at all time points. Median PSA progression free survival was 7·6 months (95% CI 6·4-9·0) and median OS was 13·5 months (95% CI 10·4-22·7). Conclusions. This LuPSMA Phase II trial provides evidence of high response rates, pain reduction and low toxicity in men with mCRPC who progressed after conventional therapies. These compelling results indicate the need for randomised trials comparing LuPSMA to existing standard-of-care.
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prostate specific membrane antigen theranostics therapy with Lutetium 177
Current Opinion in Urology, 2017Co-Authors: Justin Ferdinandus, John Violet, Shahneen Sandhu, Michael S HofmanAbstract:Purpose of reviewProstate-specific membrane antigen (PSMA) theranostics offers a new approach for a personalized and targeted treatment for metastatic prostate cancer. Lutetium-177-labelled PSMA-ligands (177Lu-PSMA) is a radionuclide therapy that is directed to PSMA expressing prostate cancer. Clini
Scott T Tagawa - One of the best experts on this subject based on the ideXlab platform.
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Lutetium 177 psma 617 for metastatic castration resistant prostate cancer
The New England Journal of Medicine, 2021Co-Authors: Oliver Sartor, Luke T Nordquist, Scott T Tagawa, Johann S De Bono, Kim N Chi, Karim Fizazi, Ken Herrmann, Kambiz Rahbar, Nitin Vaishampayan, Ghassan ElhaddadAbstract:Abstract Background Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-res...
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phase iii study of Lutetium 177 psma 617 in patients with metastatic castration resistant prostate cancer vision
Journal of Clinical Oncology, 2021Co-Authors: Michael J Morris, Luke T Nordquist, Scott T Tagawa, Johann S De Bono, Kim N Chi, Karim Fizazi, Ken Herrmann, Kambiz Rahbar, Nitin Vaishampayan, Ghassan ElhaddadAbstract:LBA4Background: Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains invariably fatal. Prostate-specific membrane antigen (PSMA) is highly expressed ...
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phase 1 2 study of fractionated dose Lutetium 177 labeled anti prostate specific membrane antigen monoclonal antibody j591 177 lu j591 for metastatic castration resistant prostate cancer
Cancer, 2019Co-Authors: Scott T Tagawa, Jaspreet S Batra, Shankar Vallabhajosula, Yuliya Jhanwar, Joseph R Osborne, Paul J Christos, Linda Lam, Himisha Beltran, Ana M MolinaAbstract:Background Prostate cancer is radiosensitive. Prostate-specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration-resistant tumors. Lutetium-177-labeled anti-PSMA monoclonal antibody J591 (177 Lu-J591) targets prostate cancer with efficacy and dose-response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely. Method Men with metastatic castration-resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts were enrolled in initial phase 1b dose-escalation cohorts followed by phase 2a cohorts treated at recommended phase 2 doses (RP2Ds) comprising 2 fractionated doses of 177 Lu-J591 2 weeks apart. 177 Lu-J591 imaging was performed after treatment, but no selection for PSMA expression was performed before enrollment. Phase 2 patients had circulating tumor cell (CTC) counts assessed before and after treatment. Results Forty-nine men received fractionated doses of 177 Lu-J591 ranging from 20 to 45 mCi/m2 ×2 two weeks apart. The dose-limiting toxicity in phase 1 was neutropenia. The RP2Ds were 40 mCi/m2 and 45 mCi/m2 ×2. At the highest RP2D (45 mCi/m2 ×2), 35.3% of patients had reversible grade 4 neutropenia, and 58.8% of patients had thrombocytopenia. This dose showed a greater decrease in prostate-specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% decrease, 29.4% with >50% decrease; median survival, 42.3 months [95% confidence interval, 19.9-64.7]). Fourteen of 17 (82%) patients with detectable CTCs experienced a decrease in CTC count. Overall, 79.6% of patients had positive PSMA imaging; those with less intense PSMA imaging tended to have poorer responses. Conclusion Fractionated administration of 177 Lu-J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, overall survival, and toxicity (dose-limiting myelosuppression) increased with higher doses.
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phase ii study of Lutetium 177 labeled anti prostate specific membrane antigen monoclonal antibody j591 for metastatic castration resistant prostate cancer
Clinical Cancer Research, 2013Co-Authors: Scott T Tagawa, Shankar Vallabhajosula, Joseph R Osborne, Matthew I Milowsky, Michael J Morris, Paul J Christos, Naveed Akhtar, Stanley J Goldsmith, Steve Larson, Neeta Pandit TaskarAbstract:Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (Lutetium-177; 177 Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177 Lu-J591 (15 patients at 65 mCi/m 2 , 17 at 70 mCi/m 2 ) with radionuclide imaging. Expansion cohort ( n = 15) received 70 mCi/m 2 to verify response rate and examine biomarkers. Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177 Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m 2 ) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. Conclusion: A single dose of 177 Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. Clin Cancer Res; 19(18); 5182–91. ©2013 AACR .
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phase ii study of Lutetium 177 labeled anti prostate specific membrane antigen monoclonal antibody j591 for metastatic castration resistant prostate cancer
Clinical Cancer Research, 2013Co-Authors: Scott T Tagawa, Shankar Vallabhajosula, Joseph R Osborne, Matthew I Milowsky, Michael J Morris, Paul J Christos, Naveed Akhtar, Stanley J Goldsmith, S M Larson, Neeta Pandit TaskarAbstract:Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (Lutetium-177; 177 Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. Experimental Design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of 177 Lu-J591 (15 patients at 65 mCi/m 2 , 17 at 70 mCi/m 2 ) with radionuclide imaging. Expansion cohort ( n = 15) received 70 mCi/m 2 to verify response rate and examine biomarkers. Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received 177 Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m 2 ) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. Conclusion: A single dose of 177 Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. Clin Cancer Res; 19(18); 5182–91. ©2013 AACR .
Justin Ferdinandus - One of the best experts on this subject based on the ideXlab platform.
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results of a 50 patient single center phase ii prospective trial of Lutetium 177 psma 617 theranostics in metastatic castrate resistant prostate cancer
Journal of Clinical Oncology, 2019Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Rodney J Hicks, Jennifer MooiAbstract:228Background: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling targeted delivery of beta...
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Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc interim results of a phase ii trial
Journal of Clinical Oncology, 2018Co-Authors: Shahneen Sandhu, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Christina Guo, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Alexis BeaulieuAbstract:5040Background: Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling tumor-targeted delivery o...
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high activity pain reduction and low toxicity with Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc results of a phase ii prospective trial
The Journal of Nuclear Medicine, 2018Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Shahneen Sandhu, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Price JacksonAbstract:531 Background: Retrospective studies demonstrate high response rates of Lutetium-177 (177Lu)-PSMA617 (LuPSMA), a radiolabelled small molecule, that binds with high affinity to prostate specific membrane antigen (PSMA) in men with mCRPC. Methods. In this phase II prospective trial, 30 pts with PSMA-avid mCRPC who had failed standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Patients were included if they had high uptake on 68Ga-PSMA PET/CT defined by tumor SUVmax greater than 1.5 times liver and were excluded if FDG PET/CT demonstrated sites of PSMA-negative disease. Administered activity (6 GBq ± 2 GBq) was adjusted according to tumor burden ( 20 sites), renal function (GFR 90 mL/min) and weight ( 90 Kg). The primary endpoints were PSA response (PCWG2) and toxicity (CTCAE v4). Other endpoints were imaging response (PCWG2 RECIST), quality of life (EORTC QLQ-C30, BPI), dosimetry, PFS and OS. Australian New Zealand Clinical Trials Registry, ACTRN12615000912583. Results. 47 men were screened to identify 30 patients eligible for treatment. 83% progressed after abiraterone and/or enzalutamide, and 87% progressed after chemotherapy including 47% following cabazitaxel. The mean administered activity was 7.5 GBq/cycle. The primary endpoint of PSA decline ≥ 50% was achieved in 17 of 30 patients (57%, 95% CI 37-75%), including 11 patients (37%, 95% CI 20-56%) with a PSA decline ≥ 80%. The most common toxicity was dry mouth in 87% of patients, all grade 1 in severity. Grade 3 or greater thrombocytopenia possibly attributed to LuPSMA occurred in 13% of patients. An objective imaging response was seen in 82% of the subgroup of 17 patients who had evaluable soft tissue disease. The overwhelming pattern of progression was seen in non-target marrow disease. Pain severity and interference scores improved significantly at all time points. Median PSA progression free survival was 7·6 months (95% CI 6·4-9·0) and median OS was 13·5 months (95% CI 10·4-22·7). Conclusions. This LuPSMA Phase II trial provides evidence of high response rates, pain reduction and low toxicity in men with mCRPC who progressed after conventional therapies. These compelling results indicate the need for randomised trials comparing LuPSMA to existing standard-of-care.
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prostate specific membrane antigen theranostics therapy with Lutetium 177
Current Opinion in Urology, 2017Co-Authors: Justin Ferdinandus, John Violet, Shahneen Sandhu, Michael S HofmanAbstract:Purpose of reviewProstate-specific membrane antigen (PSMA) theranostics offers a new approach for a personalized and targeted treatment for metastatic prostate cancer. Lutetium-177-labelled PSMA-ligands (177Lu-PSMA) is a radionuclide therapy that is directed to PSMA expressing prostate cancer. Clini
Amir Iravani - One of the best experts on this subject based on the ideXlab platform.
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Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies
Prostate Cancer and Prostatic Diseases, 2020Co-Authors: Amir Iravani, John Violet, Arun Azad, Michael S HofmanAbstract:Theranostic principles utilize a molecular biomarker specific for a tumor target, initially for imaging to assess target expression and, if deemed suitable, for targeted therapy. This presents an exciting opportunity for a highly personalized treatment strategy in the era of precision medicine. Prostate-specific membrane antigen (PSMA) theranostics has attracted increasing attention as a promising targeted treatment in metastatic prostate cancer (PC). ^177Lu-DOTA-PSMA-617 (^177Lu-PSMA-617) is a PSMA-targeted small molecule with favorable properties and is the most extensively investigated PSMA radioligand for radionuclide therapy (RNT) in PC. Since 2014 multiple retrospective studies and more recently a phase II prospective study demonstrated safety and impressive efficacy of ^177Lu-PSMA RNT. The evidence generated by these trials led to two currently underway randomized trials in metastatic castrate-resistant PC: TheraP (NCT03392428) and VISION (NCT03511664). While we wait for these pivotal trials to read out, nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists are facing a steep learning curve to master the intricacies and nuances of this novel therapeutic strategy. This review article aims to share and discuss the evolving experience in practical aspects of PSMA theranostics.
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results of a 50 patient single center phase ii prospective trial of Lutetium 177 psma 617 theranostics in metastatic castrate resistant prostate cancer
Journal of Clinical Oncology, 2019Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Rodney J Hicks, Jennifer MooiAbstract:228Background: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling targeted delivery of beta...
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Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc interim results of a phase ii trial
Journal of Clinical Oncology, 2018Co-Authors: Shahneen Sandhu, Amir Iravani, John Violet, Justin Ferdinandus, Sueping Thang, Christina Guo, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Alexis BeaulieuAbstract:5040Background: Lutetium-177 (177Lu)-PSMA617 (LuPSMA) is a radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling tumor-targeted delivery o...
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high activity pain reduction and low toxicity with Lutetium 177 psma617 theranostics in metastatic castrate resistant prostate cancer mcrpc results of a phase ii prospective trial
The Journal of Nuclear Medicine, 2018Co-Authors: Michael S Hofman, Amir Iravani, John Violet, Justin Ferdinandus, Shahneen Sandhu, Sueping Thang, Grace Kong, Aravind Ravi S Kumar, Tim Akhurst, Price JacksonAbstract:531 Background: Retrospective studies demonstrate high response rates of Lutetium-177 (177Lu)-PSMA617 (LuPSMA), a radiolabelled small molecule, that binds with high affinity to prostate specific membrane antigen (PSMA) in men with mCRPC. Methods. In this phase II prospective trial, 30 pts with PSMA-avid mCRPC who had failed standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Patients were included if they had high uptake on 68Ga-PSMA PET/CT defined by tumor SUVmax greater than 1.5 times liver and were excluded if FDG PET/CT demonstrated sites of PSMA-negative disease. Administered activity (6 GBq ± 2 GBq) was adjusted according to tumor burden ( 20 sites), renal function (GFR 90 mL/min) and weight ( 90 Kg). The primary endpoints were PSA response (PCWG2) and toxicity (CTCAE v4). Other endpoints were imaging response (PCWG2 RECIST), quality of life (EORTC QLQ-C30, BPI), dosimetry, PFS and OS. Australian New Zealand Clinical Trials Registry, ACTRN12615000912583. Results. 47 men were screened to identify 30 patients eligible for treatment. 83% progressed after abiraterone and/or enzalutamide, and 87% progressed after chemotherapy including 47% following cabazitaxel. The mean administered activity was 7.5 GBq/cycle. The primary endpoint of PSA decline ≥ 50% was achieved in 17 of 30 patients (57%, 95% CI 37-75%), including 11 patients (37%, 95% CI 20-56%) with a PSA decline ≥ 80%. The most common toxicity was dry mouth in 87% of patients, all grade 1 in severity. Grade 3 or greater thrombocytopenia possibly attributed to LuPSMA occurred in 13% of patients. An objective imaging response was seen in 82% of the subgroup of 17 patients who had evaluable soft tissue disease. The overwhelming pattern of progression was seen in non-target marrow disease. Pain severity and interference scores improved significantly at all time points. Median PSA progression free survival was 7·6 months (95% CI 6·4-9·0) and median OS was 13·5 months (95% CI 10·4-22·7). Conclusions. This LuPSMA Phase II trial provides evidence of high response rates, pain reduction and low toxicity in men with mCRPC who progressed after conventional therapies. These compelling results indicate the need for randomised trials comparing LuPSMA to existing standard-of-care.
