THERANOSTIC ROLE OF NUCLEAR MEDICINE

Vikas Prasad

Vice Chair and Senior Physician

Department of Nuclear Medicine

University Hospital of Ulm

Germany

DISCLOSURE OF INTEREST

Ipsen: Consultant

ITM: Consultant

Theranostics is a portmanteau of therapeutics and diagnostics.Theranostics is a proposed diagnostic methodology for personalizing therapeutic intervention/s

Theranostic Concept in Nuclear Medicine

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

Methods for the identification of primary and metastatic

gastroenteropancreatic NETs

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

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

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

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

Peptide Receptor Radionuclide Therapy

14

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

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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.

Safety and Tolerability(No. of patients (%), Safety Set; n=221)

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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

ToxicityBodei, Kidd, Prasad, Modlin

Front Horm Res. 2015;44:198-215

J Clin Oncol 36:2578-2584

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

Thank You For Your Attention