A first NZ Study Looked at the Role of Lutetium-177- PSMA I&T in the Progression of Metastatic
Castration-Resistant Prostate Cancer (mCRPC)
Presented by Madhusudan Vyas
Organisation/s: Mercy Radiology, Unitec Institute of Technology and AUT, Auckland Presented at NZIMRT Auckland branch, study day
Date: 23.07.2022
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
Epidemiology (Global data)
Siegel R et al. CA Cancer J Clin 2013; 63:11-30
Epidemiology (NZ Data)
• 25,000 NZ men are currently living with a diagnosis of prostate cancer (MOH,2018)
• 3000 new cases are being diagnosed with prostate cancer, each year
• 560 are likely to die each year from metastatic prostate cancer
Important to note:
• 60% of these cases already have metastatic disease at the time of their first diagnosis
• This indicates that early detection is being missed
Diagnosis and staging
Ref:
Parker, C., Gillessen, S., Heidenreich, A., & Horwich, A.
(2015). Cancer of the prostate: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up. Ann
Oncol, 26 Suppl 5 , v69-77. doi:10.1093/annonc/mdv222
Treatment plan
Ref: Parker, C., Gillessen, S., Heidenreich, A., & Horwich, A. (2015). Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol, 26 Suppl 5 , v69-77. doi:10.1093/annonc/mdv222
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 disease(mCRPC) treatment algorithm
Ref: Cancer of the prostate: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up, Parker C, Gillessen S, Heidenreich A and Horwich A, Ann Oncol 2015;
26 (Suppl63): v69-v77.
Author and year No. of patient treated Median age (In years)
PSA declined (>50%)
Remission of disease (%) Overall survival (Months)
Azad et al., 2015 68 72 15/68 - 11
Cheng et al., 2015 165 62 28/165 12 8
Caffo et al., 2015 49 75 12/49 15 10
Brasso et al., 2015 137 71 22/122 12 8
Badrising et al., 2016 102 - 26/102 - 12
Davies, Smith, &
Lester, 2016
34 69 - - 10
de Bono et al., 2018 69 70 16/57 - 11
Loriot et al., 2013 38 71 3/38 12 12
Noonan et al., 2013 30 70 16/57 - 13
Pezaro et al., 2014 36 62 16/36 15 16
Sella et al., 2014 24 65 6/19 15 8
Metastatic disease(mCRPC) treatment review of literature
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
PS M A
mCRPC cell
rec ep to r
LU -177 PS M A LU -177 PS M A LU -177 rec ep to r
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
Another one in same year……
Lu-177 PSMA based Metastatic disease(mCRPC) treatment review of literature
Author and year No. of patient Treated
Median age (year) range
Radio ligand PSA Decline
(>50%)
Remission of
disease (%) Overall survival (Months)
Bander et al., 2005 35 68 J519 4/35 - -
Tagawa et al., 2013 47 74 J519 5/47 8 17
Heck et al., 2016 22 71 I&T 6/18 5 -
Kratochwil et al., 2016 30 73 617 13/30 - -
Ahmadzadehfar et al., 2016 52 71 617 31/52 - 14
Fendler et al., 2016 15 73 617 7/12 27 -
Bräuer et al., 2017 59 72 617 24/41 - 8
Rahbar et al., 2018 145 73 617 49/99 - -
Scarpa et al., 2017 10 64 617 5/10 30 -
Yadav et al., 2017 31 65 617 22/31 82 16
Emmett et al., 2019 14 69.5 617 10/14 - -
Rahbar et al., 2018 104 70 617 34/104 - 14
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
Saline I/V infusion, lemon drink and
anti nausea medicine prior to
Therapy
Infusion of Lu- 177-PSMA-I&T over 30 minutes
Immediate post Infusion injection
of diuretic and additional IV
Saline
Discharge patient after minimum of 3
hours and satisfactory radiation exposure
reading
Post 24 hrs
SPECT-CT scan
• 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=97) 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 97
Time period August 2018 to December 2021
Completed 4 cycles of treatment (responder) n=43
Completed 2 cycles of treatment (non responder) n=53
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=94), Grade 1 (n=1),Grade 2 (n=1) Anaemia: Grade 0 (n=93), Grade 1 (n=4),Grade 3 (n=1) Leukocytopenia: Grade 0 (n=94), Grade 1 (n=3),Grade 2 (n=1)
Side effects n=20 reported Nausea
n=19 Lethargic
n=58 dry mouth post therapy
Death during treatment No, 1 patient died after a fall (1x infusion)
Response PSA
PSA response
50.51% Patients PSA responded more than 50% reduction from the baseline value
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
Quality of Life Outcomes
%Changes from baseline
FACT-P Changes
55.25% Patients reported improvement in general health
%Changes from baseline
60.58% Patients reported improvement in
overall treatment outcome
50.51% Patients reported improvement in Prostate cancer related quality of life aspects
%Changes from baseline
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
Patient survival post-treatment
6 months 12 months 18 months 24 months
69.50% 34% 20% 9%
0 20 40 60 80 100 120
total number of
patients alive at 6 months alive at 12 months alive at 18 months alive at 24 months
survival scale per 6 months interval
number of alive patients
Experiences of patients
Treatment outcome related feedback
“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”
“So we’re very relieved that he didn’t have any side effects”
“I was on steroids before, at the start of this treatment. And I just stopped those myself…”
Financial status and Healthcare system related feedback
“And in the end, with no more treatment, no more medication through the public system, it was left for the cancer to take hold of, where it was and come back type thing…”
“I guess the only downside to that treatment is it’s quite expensive….”
“it’s like, I look to tomorrow, because that’s where I spend the rest of my life….”
“yeah it is a big decision, but like I said before, it’s, we were lucky we had the money to do it….”
Life status feedback
“ And it’s really, it’s not a cure. It’s a treatment that extends your life…”
“Now there’s no real impact at all on the people around you, because the quality of life’s improved so much…”
“But at the moment, I’m okay, but it has improved my general wellbeing and the outlook on things over the last, oh
how long have I been involved? Six months or more… ”
Image evaluation for therapy responses
Pre therapy Ga68-PSMA scan Post therapy Ga68-PSMA scan
Images provided by Mercy Radiology
Image evaluation for therapy responses
Pre therapy Ga68-PSMA scan Post therapy Ga68-PSMA scan
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
Why 177-Lu is considered to be a game changer in the theranostic approach?
A. Due to its global availability B. Long enough half life
C. High excretion from the kidney
D. Long half life, dual energy emitter ( beta and gamma radiation) and
optimum tissue penetration
Answer is:
D. Long half life, dual energy emitter ( beta and gamma radiation) and
optimum tissue penetration
A 65-year-old man complains of nausea for the previous three days when he visits the clinic. The patient had treatment with a radioligand therapy based on 177Lu-PSMA- I&T a week before the onset of these symptoms. Additionally, the patient feels fatigued and has a dry mouth. He is admitted with a low-grade temperature, 95 beats per minute pulse, 120/78 mm Hg blood pressure, and 15 breaths per minute respiratory rate. Which of the following reasons for the patient's clinical presentation will you consider?
A. Radionuclide therapy based side effects B. Androgen hormone therapy impacts
C.Cumulative impact of the ongoing and past therapies
D.Nothing related to the ongoing or past treatment
A. Radionuclide therapy based side effects
Answer is:
Now you have any Question ??
