theranostic role of nuclear medicine...theranostic role of nuclear medicine vikas prasad vice chair...
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THERANOSTIC ROLE OF NUCLEAR MEDICINE
Vikas Prasad
Vice Chair and Senior Physician
Department of Nuclear Medicine
University Hospital of Ulm
Germany
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DISCLOSURE OF INTEREST
Ipsen: Consultant
ITM: Consultant
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Theranostics is a portmanteau of therapeutics and diagnostics.Theranostics is a proposed diagnostic methodology for personalizing therapeutic intervention/s
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Theranostic Concept in Nuclear Medicine
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Radiopharmaceuticals-NET
SomatostatinReceptors (SRS)
Serotonin ProductionPathways-C-11 5HTP
Biogenic Amines-
F-18 DOPA
Glucose MetabolismF-18 FDG
Because of the heterogeneity of neuroendocrine tumors in their
functionality, their origin and prognoses,there are overlapping zones amongst the
targets for molecular imaging.
Major Target
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Methods for the identification of primary and metastatic
gastroenteropancreatic NETs
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Somatostatin-Receptor Imaging
l For imaging somatostatin receptor positive tumor
l SPECT/ PET-Ligand: R-Affinity
l DTPA-Octreotide (ssr2↑, ssr5↑)
l DOTA-Tyr3-Octreotide (DOTA-TOC) (ssr2↑, ssr3↓, ssr5↑↑)
l DOTA-Tyr3-Octreotate (DOTA-TATE) (ssr2↑↑, ssr5↓)
l DOTA-1-Nal3-octreotide (DOTA-NOC) (ssr2↑↑, ssr3↑, ssr5↑)
l DOTA-JR11 (antagonist)
l Radioisotopes
l SPECT Tc-99m, In-111
l PET Ga-68
Ga-68 DOTATOC and Ga-68 DOTATATE approved
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Ga-68 SRS PET/CT (3-phase) CUP
a b c
Ileum NET confirmed on
surgery
Detection Rate 50-59%
Prasad V, et al. Eur J Nucl Med Mol Imaging. 2010
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Well differentiated, G1/G2 NET,
Proliferation Rate <20%
Pancreatic NET
Insulinoma
MEN-1SSR PET/CT combined with Endosonography
Ga-68 Exendin combined with endosonography
Sporadic
SSR PET/CT combined with Endosonography
Others SSR PET/CT
Ileum
Functional (serotonin producing)
SSR PET/CT
SSR –ve lesions / clinical suspicion –
F-18 DOPA PET/CT
Non functional SSR PET/CT
Rectal
Purely NET SSR PET/CT
Mixed (adeno-neuroendocrine
component)
Role of SSR PET/CT doubtful
CUP, other NET SSR PET/CT
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G3 NET, Proliferation Rate
> 20%
If PRRT is under consideration
SMS-R PET/CT
FDG PET/CT
If PRRT is not under
considerationFDG PET/CT
For G3 NEC; CT or MRI are sufficient, in some cases FDG PET/CT for
correct staging might be needed
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Peptide Receptor Radionuclide Therapy
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Aim
Design International, multicenter, randomized, comparator-controlled, parallel-
group
Evaluate the efficacy and safety of 177Lu-Dotatate + SSAs (symptoms
control) compared to Octreotide LAR 60mg (off-label use)1 in patients with
inoperable, somatostatin receptor positive, midgut NET, progressive under
Octreotide LAR 30mg (label use)
Baseline and
Randomization
n = 115
Dose 1
n = 115
Treatment and AssessmentsProgression free survival (RECIST criteria) every 12 weeks
5 Years
follow
up
Dose 2 Dose 3 Dose 4
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NETTER -1 Study Objectives and Design
1. FDA and EMA recommendation
4 administrations of 7.4 GBq of 177Lu-Dotatate every 8 weeks + SSAs (symptoms control)
Octreotide LAR (high dose - 60mg every 4 weeks1)
Slides Dr. J Strosberg N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
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N = 229 (ITT)
Number of events: 90
• 177Lu-Dotatate: 23
• Oct 60 mg LAR: 67
15
All progressions centrally confirmed and independently reviewed for eligibility (SAP)
Progression-Free Survival
Octreotide LAR 60 mg
Median PFS: 8.4 months
177Lu-Dotatate
Median PFS: Not reached
Hazard ratio : 0.21 [0.129 –
0.338] p < 0.0001
79% reduction in the risk
of disease
progression/death
Estimated Median PFS in
the Lu-DOTATATE arm
≈ 40 months
Slides Dr. J Strosberg N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
Median OS 27.4 months in Oct arm
In PRRT arm median OS not reached
Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 4099-4099
DOI: 10.1200/JCO.2018.36.15_suppl.4099
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Objective Responsescurrently evaluable patients
177-Lu-Dotatate(n=101)*
Sandostatin LAR 60 mg (n=100)*
Complete Response (n) 1 0
Partial Response (n) 17 3
Objective Response Rate (*) 18% 3%
Confidence Interval (95%) 10% - 25% 0% - 6%
Statistical Significance p = 0.0008
All patients (n=116) (n=113)
Progressive Disease 6 (5%) 27 (24%)
Stable Disease 77 (66%) 70 (62%)
(*) Exclude patients with no post-baseline scans or central response available
Slides Dr. J StrosbergN Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
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Safety and Tolerability(No. of patients (%), Safety Set; n=221)
17
177-Lu-Dotatate(n=111)
Octreotide LAR 60mg (n=110)
Any adverse event 106 (96%) 95 (86%)
Related to treatment 95 (86%) 34 (31%)
Serious adverse events 29 (26%) 26 (24%)
Related to treatment 10 (9%) 1 (1%)
Withdrawals due to adverse events 7 (6%) 10 (9%)
Related to treatment 5 (5%) 0 (0%)
Slides Dr. J Strosberg
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Creatinine Clearance
0
20
40
60
80
100
120
Baseline Wk 4 Wk 12 Wk 24 Wk 36 Wk 48 Wk 60 Wk 72 Wk 84 Wk 96
Lutathera
Sando 60 mg
Cre
atin
ine
Cle
aran
ce -
mea
n (
mL
/min
)
177Lu-Dotatate
Octreotide 60 mg
n = 106/96 99/93 100/91 77/61 63/39 52/26 36/14 27/8 14/3 8/3
Slides Dr. J Strosberg
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ToxicityBodei, Kidd, Prasad, Modlin
Front Horm Res. 2015;44:198-215
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J Clin Oncol 36:2578-2584
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J Clin Oncol 36:2578-2584
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ENETS Guideline-Management of Liver
Metastases from G1-G2 NEN
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Therapy Options for Advanced Stage NEN
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Therapy Options Pancreas NEN
COMPETE Study
PRRT with Lu-177 DOTATOC vs
Everolimus
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Thank You For Your Attention