A first New Zealand study looked at the role of Lutetium-177-PSMA I&T in the progression of metastatic castrate-resistant prostate cancer
• Madhusudan Vyas, Jessica Fagan, Dr Nick Garett and Dr Remy Lim
• Organization/s:
Unitec institute of Technology, Mercy Radiology and AUT University,
Auckland
• CMT Virtual conference-2021
Objectives
▪ To assess the efficacy of Lutetium-177-PSMA-I&T therapy to palliate end stage mCRPC
▪ To review tolerability and impact on QOL of Lutetium-177-
PSMA-I&T therapy
Metastatic Castration resistant prostate cancer (mCRPC)
A proportion of prostate cancer patients will continue to progress following systemic treatment and cease to respond to hormonal manipulation or chemotherapy
Features:
• No response to Androgen deprivation therapy (ADT)
• Continuous rise in the PSA value
• Metastatic spread to bone, lymph nodes and visceral organs
• Reduction in the overall survival rate of patients
• Life expectancy of the patients’ usually 14-16 months
Metastatic Castration resistant prostate cancer (mCRPC) and PSMA
• 90-95% metastatic prostate cancer cells expresses Prostate specific membrane antigen (PSMA) transmembrane protein
• PSMA can be a target for imaging and treatment of prostate cancer
• Lu-177 PSMA therapy currently only available privately
Ga-68-PSMA-11
Lu-177-PSMA-I&T
Various PSMA ligands and radionuclides suitable for labelling
J591
PSMA-617
PSMA-I&T
PSMA ligands in use currently
PSMA
mCRPC cell
recep tor
LU -177 PSMA LU -177 PSMA LU -177 recep tor
Lu-177-PSMA-I&T delivers DNA damaging
radiation directly to the site of disease and kills the metastatic cells only
Lu177-PSMA and Mechanism of
therapy
Lu 177 -PSMA
First reported outcome for Lu177-PSMA-617
Afshar-Oromieh, Kratochwil, et al., Department of Nuclear Medicine, University Hospital Heidelberg
Inclusion criteria
• Patients diagnosed with castrate-resistant, progressive metastatic prostate cancer following conventional systemic treatment.
• PSMA expressing tumour confirmed with baseline Ga68-PSMA PET/CT scan
• Life expectancy of at least 6 months
• White cell count (WBC) (Normal range 4.0-11.0X109/L)
• Haemoglobin (Hb) (Normal range 130-175 g/L)
• Platelets (Normal range 150-400X109/L)
• Creatinine (micro mol/L)
• eGFR (>90 mL/min/1.73m2)
• No renal outflow obstruction
• Eastern Cooperative Oncology Group (ECOG) performance status score <2
Exclusion criteria
• Low level or minimal PSMA expression in their tumour
• Diffuse marrow disease deemed to be at high risk of marrow failure with therapy or marrow failure
• Reduced renal function/renal obstructive outflow
Identified patient
End stage mCRPC
PSMA avid disease PSA progression
Follow up Ga68 PSMA-
11 PET-CT scan and PSA status
Follow up Ga68 PSMA-
11 PET-CT scan and PSA status
2 nd Tx
1 st Tx 3 rd Tx 4 th Tx
Each Tx delivered with a gap of 6-8 weeks
Treatment protocol
Treatment protocol
• Biochemical response: PSA response (>50% reduction from baseline)
• Imaging response: Reduction in SUV of lesions on interim PSMA PET/CT
Response criterion
Results: Patient Characteristics
Characteristics (n=18) Average
Age (year) 69.36 (51-81)
PSA (ug/L) 139.72(0.23-1310 ug/L)
Haemoglobin (g/L) 119.89 (77-145 g/L)
eGFR (mL/min/1.73m 2 ) 76.38 (53- 90 mL/min/1.73m 2 ) Creatinine (mol/L) 80.10 (43-118 mol/L)
Platelets count (/L) 258.23 (125-396 X10 9 /L)
WBC (/L) 6.81 (4.2-12.3X10 9 /L)
ECOG Performance status 1 (0-1)
Results: Therapy outcomes
Total number of patient treated 18
Time period August 2018 to August 2019
Completed 4 cycles of treatment (responder) n=13
Completed 2 cycles of treatment (non responder) n=4
Completed 1 cycle of treatment (patient died after 1 x cycle)
n=1
Nephrotoxicity No significant change in renal function observed
Haematoxicity Thrombocytopenia: Grade 0 (n=16), Grade 1 (n=1),Grade 2 (n=1) Anaemia: Grade 0 (n=13), Grade 1 (n=4),Grade 3 (n=1) Leukocytopenia: Grade 0 (n=14), Grade 1 (n=3),Grade 2 (n=1)
Side effects n=2 reported Nausea
n=3 Lethargic
n=13 dry mouth post therapy
Death during treatment No, 1 patient died after a fall (1x infusion)
PSA Response
-150.00%
-100.00%
-50.00%
0.00%
50.00%
100.00%
150.00%
200.00%
250.00%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
PSA response after 2 to 4 cycles of Treatment
>50% reduction of PSA 10/18 patients
(58% response rate)
78%
17%
0%
5%
0%
Leukocytopenia
Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 84%
6%
5% 5%
0%
Thrombocytopenia
Grade 0 Grade 1 Grade 2 Grade 3 Grade 4
Haematoxicity
72%
22%
0%
6%
0%
Anaemia
Grade 0 Grade 1 Grade 2 Grade 3 Grade 4
-20 -15 -10 -5 0 5 10 15 20 25
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
%Changes from baseline
Patients
FACT-G changes
FACT-G changes
-30 -20 -10 0 10 20 30 40 50 60
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
%Changes from baseline
Patients
TOI changes
TOI…
70.58% Patients shows high treatment outcome index
-30.00 -20.00 -10.00 0.00 10.00 20.00 30.00 40.00
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Axis Title
Axis Title
FACT-P Changes
FACT-P Changes
58.82% Patients reported improvement in prostate related general health
Quality of Life Outcomes
70.58% Patients reported
improvement in general health
Quality of Life Outcomes
-20 -10 0 10 20 30 40 50 60
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Physical well being (PWB)
82.35% Patients reported improvement in PWB
-15 -10 -5 0 5 10 15 20 25
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Social well being (SWB)
23.52% Patients reported improvement in SWB
-30 -20 -10 0 10 20 30
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Emotional well being (EWB)
64.70% Patients reported improvement in EWB
-40 -20 0 20 40 60 80
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Functional well being (FWB)
47.05% Patients reported improvement in PWB
Quality of Life Outcomes
80%
20%
0%
QoL of patients who received 2 cycles of Treatment
Better No change Worse
62%
23%
15%
QOL for patients who received 4 cycles of Treatment
Improved
Average
Worse
“This treatment I found far better in comparison of the chemotherapy in terms of experiences..”
“ I haven’t felt any change in my daily routine, this treatment is really comfortable and less worse in comparison of my other previous
treatments…”
“ It is pain less, stress less and a better experience every time in comparison of my previous treatment.”
Feedback from patients
Image evaluation for therapy responses
Pre therapy Ga68-PSMA scan Post therapy Ga68-PSMA scan
Image evaluation for therapy responses
Pre therapy Ga68-PSMA scan Post therapy Ga68-PSMA scan
Limitations
• Single arm study
• No follow up for delayed toxicity
• No long term follow up
Future plan
• Involve Control group
• More in depth evaluation of QoL using face to face interview of treated patients
• Longer term follow up of patients to evaluate for delayed toxicity
and survival
Conclusion
• Lu177-PSMA-I&T is safe and effective in palliating patients with end- stage mCRPC patients
• Majority of patients experienced an improved quality of life whilst on
treatment
Our team
References
• Ahmadzadehfar, H., Essler, M., Schafers, M., & Rahbar, K. (2016). Radioligand therapy with (177)Lu-PSMA-617 of metastatic prostate cancer has already been arrived in clinical use. Nucl Med Biol, 43(12), 835. https://doi.org/10.1016/j.nucmedbio.2016.08.003
• Aus, G., Abbou, C. C., Bolla, M., Heidenreich, A., Schmid, H. P., van Poppel, H., . . . Zattoni, F. (2005). EAU guidelines on prostate cancer. Eur Urol, 48(4), 546-551.
https://doi.org/10.1016/j.eururo.2005.06.001
• Azad, A. A., Eigl, B. J., Murray, R. N., Kollmannsberger, C., & Chi, K. N. (2015). Efficacy of enzalutamide following abiraterone acetate in chemotherapy-naive metastatic castration- resistant prostate cancer patients. Eur Urol, 67(1), 23-29. https://doi.org/10.1016/j.eururo.2014.06.045
• Baccala, A., Sercia, L., Li, J., Heston, W., & Zhou, M. (2007). Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms. Urology, 70(2), 385-390. https://doi.org/10.1016/j.urology.2007.03.025
• Badrising, S. K., van der Noort, V., van den Eertwegh, A. J., Hamberg, P., van Oort, I. M., van den Berg, H. P., . . . Bergman, A. M. (2016). Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation. Prostate, 76(1), 32-40.
https://doi.org/10.1002/pros.23094
• Bander, N. H., Milowsky, M. I., Nanus, D. M., Kostakoglu, L., Vallabhajosula, S., & Goldsmith, S. J. (2005). Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol, 23(21), 4591-4601. https://doi.org/10.1200/jco.2005.05.160
• Baum, R. P., Kulkarni, H. R., & Albers, P. (2017). Theranostics: PSMA ligands for molecular imaging and radionuclide therapy of advanced prostate cancer. Onkologe, 23(8), 597‐608. https://doi.org/10.1007/s00761-017-0246-2
• Bouchelouche, K., Choyke, P. L., & Capala, J. (2010). Prostate specific membrane antigen- a target for imaging and therapy with radionuclides. Discov Med, 9(44), 55-61.
• Brasso, K., Thomsen, F. B., Schrader, A. J., Schmid, S. C., Lorente, D., Retz, M., . . . de Bono, J. (2015). Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis. Eur Urol, 68(2), 317-324. https://doi.org/10.1016/j.eururo.2014.07.028
• Bräuer, A., Grubert, L. S., Roll, W., Schrader, A. J., Schäfers, M., Bögemann, M., & Rahbar, K. (2017). 177Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging, 44(10), 1663-1670. https://doi.org/10.1007/s00259-017-3751-z
• Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6), 394-424. https://doi.org/10.3322/caac.21492
