cTACE Mixing & Injection System

Vectorio efficacy & safety for improved cTACE mixing & delivery®

24Device functionality verified
up to 24h in contact with Lipiodol®

U n b r e a k a b l e | U s e r - F r i e n d ly | S h a r p

Contents

Primary liver cancer epidemiology• 782,000 new cancer cases worldwide occurred in 2012 (1)P3Primary liver cancer epidemiology

P4

Lipiodol® indication in HCC• 2nd most common cause of death from cancer worldwide, 746,000 deaths in 2012 (1)P5BCLC staging system & treatment strategy• HCC represents more than 90% of primary liver cancers (2)P6Dual arterial & venous perfusion for efficient cTACE

P7

Overall survival data

P8Vectorio® intended use

P9Vectorio® Compounds

P 10 Vectorio® Set
P 14 Lipiodol® Ultra Fluid - anticancer drug mixture preparation using Vectorio®

• 5th most common cancer in men (554,000 cases) and the 9th in women (228,000 cases) (1)• Very poor prognosis

Incidence

Mortality

782,000

746,000

out of 782,000 cases

554,000
228,000

95%

P 16 Features & benefits of Vectorio®
P 17 Bibliography
PRIMARY LIVER CANCER - A DEADLY DISEASE

2-3

Lipiodol® indication in HCC

BCLC staging system & treatment strategy (2)
HCC

Tumor

Visualization, Localization and Vectorization during
Trans‑Arterial Chemoembolization (TACE) of hepatocellularcarcinoma (HCC) at intermediate stage, in adults

LiverAorta
Hepatic artery• HCC etiology- Hepatitis B & C- Prolonged alcohol abuse- Non alcoholic steato hepatitis (NASH)• Conventional Trans Arterial Chemoembolization (cTACE)- cTACE = Lipiodol® TACE- Intratumor injection of Lipiodol® + anticancer agent- Complementary embolization with gelatin sponge		 or particles
Lipiodol® +anticancer drug

Stage A-C

Stage DPST 0-2, Child-Pugh A-B

PST >2, Child-Pugh C*

Iliac artery
Micro-catheter

Very early stage (0)Early stage (A)Intermediate stage (B)Advanced stage (C)Single < 2 cm,Carcinoma in situ

Single or 3 nodules ≤ 3 cm, PS 0

Multinodular, PS 0

Portal invasion,
N1, M1, PS 1-2

Terminal stage (D)Single3 nodules ≤ 3 cm

TACESorafenib

Best supportive care

Target: 20%
OS: 20 mo (45-14)

Target: 40%
OS: 11 mo (6-14)

Target: 10%
OS: < 3 mo

Portal pressure/bilirubin

Vectorio®

Embolic material

Increased

Tumor necrosis & size reduction

Associated diseases

NormalNoYes

Resection

Liver transplantation(CLT/LDLT)

RF/PEI

Curative treatment (30-40%)
Median OS > 60 mo; 5-yr survival: 40-70%

CatheterCancerous tumor

Stage 0
PST 0, Child-Pugh A

Cancerous tumor

BCLC = Barcelona-Clinic Liver Cancer

LIPIODOL® - INDICATED TO FIGHT HCC

4-5

cTACE: "standard-of-caRe" for stage B hcc patients

Dual arterial & venous perfusion for efficient cTACE (3)Overall survival data (2, 4)• Radiological evidence of dual vascularization of HCC

HCCHCCHCC
CatheterCatheter

Catheter

16

Grade 0

Grade 1

Grade 2

Arterial enhancementof the tumor

Early venous enhancement
thanks to the peribiliary vascular plexa

Full visualization of thearterioportal vascular bed

months20months

Grade 0

Grade 1

Grade 2

Grades of portal vein visualization & size of tumors treated with ultraselective cTACEPERIBILIARY PLEXA ALLOW LIPIODOL®-DRUG DROPLETSSHUNTING FROM HEPATIC ARTERY TO PORTAL VEIN

6-73745months
SIGNIFICANT IMPROVEMENT OF STAGE B HCC PATIENT OVERALL SURVIVAL

intented use

24LipiodoL® Resistant Mixing & Injection System forconventional Trans-Arterial Chemo-Embolization (cTACE)
Lipiodol® Ultra Fluid - anticancer mixture should be performed withcompounds
Raw materials of Vectorio® have been validated for resistance to Lipiodol® up to 24h
A & B 20 mL mixing syringes (x2)

Device functionality verified
up to 24h in contact with Lipiodol®

*F

D Lipiodol® Ultra Fluid ampoule withdrawing straw (x1)

GE *Lipiodol® Ultra Fluid vial spike (x1)

Mixture preparation recommendations**• Vigorous mixing of Lipiodol® & anticancer drug via the stopcock

AF 3-way stopcock with 4 connections (x1)BH• Anticancer drug should be first pushed towards the syringe containing Lipiodol®
• Anticancer drug volume should be lower than Lipiodol® volume, ideally 1 drug volume to 2 Lipiodol® volumes

C Particle filter for Lipiodol® Ultra Fluid withdrawal (x1)

G Connector (x1)
EH 1 mL injection syringe (x1)

II 3 mL injection syringe (x1)
DLipiodol® Ultra Fluid may be associated with various anticancer drugs
CAnticancer drugs that may be associated with L ipiodoL ® U ltra F luid***Cisplatin

Doxorubicin

Epirubicin*Guerbet recommends the use of Vectorio® to prepare and inject the mixture of Lipiodol® and anticancer drug**Th. De Baère et al. Cardio. Vasc. Radiol. 2016***The instructions and precautions for use relating to anticancer drugs must be strictly followed

8-9

Mitomycin* Guerbet project under progress

The system does not contain:• Lipiodol® Ultra Fluid ampule or vial
• Anticancer drug
• MicrocatheterSet24Mixing syringes (20 mL)

Design Aim - Making multiple mixes easy & safe

24Injection syringe (1 mL & 3 mL)

Device functionality verified
up to 24h in contact with Lipiodol®

Design Aim - Making injection easy & safe

Device functionality verified
up to 24h in contact with Lipiodol®

Plunger -- Ergonomic design for optimal grip and easy injection
Plunger -- Ergonomic convex shape, rotatable, atraumatic for the palm & fingers
Backstop (Patented) -- Prevents accidental release & uncontrolled drug exposure

Backstop (Patented) -- Prevents accidental release & uncontrolled drug exposure
Rotary finger support -- Obtain more suitable working position

Rotary finger support -- Adjustable working position after connection• O-ring design -- Sealing function• Elimination of the elastic zone -- Tactile feedback improvement, direct transmissionof forces from hand to mixture

10-11• O-ring design -- Sealing function• Elimination of the elastic zone -- Tactile feedback improvement, direct transmissionof forces from hand to emulsion

24
3-way stopcock with 4 connections-(Patented)
Design Aim - Easy & safe to perform operation

Device functionality verified
up to 24h in contact with Lipiodol®

24Particle filter forwithdrawing Lipiodol®

Double female
connector

Design Aim - Easy & safe to perform preparation

Raw materials - Strong & Resistant for cTACE use
Catheter/patient line connection• Connects 2 mixing syringes,
Injection syringe & catheter• The "L" channel & Rotary handle enable tochose which two ports can be connected

Mix, inject, refill or remix
No need to disconnect

Foolproof Luer lock connection
Mixing ports

12-13Injection port

• Vectorio� mixing syringes can't be connected to injection port
• Mixing ports can't communicate with the patient

15µm filter retain glass
particles that may
be released when
breaking ampoule

Transfer drug fromthe pharmaceuticalpreparation syringe
to the mixing syringeof Vectorio®

Device functionality verified
up to 24h in contact with Lipiodol®

Lipiodol® Ultra Fluid - anticancer drug mixture preparation using
STEP I: W ithdrawing

STEP II: M ixing

STEP III: I njecting

1st1 drug volumeTO2 Lipiodol® volumes 5	Withdraw Lipiodol® Ultra Fluid and anticancer
drug into the 2 mixing syringes	Connect the mixing syringes to the
4 ports 3 way stopcock nticancer drug should beA
first pushed towards thesyringe containing Lipiodol® 5P erform 20 vigorous back & forth movements
to obtain an homogeneous mixture 5

Connect stopcock to the microcatheterLipiodol® Ultra Fluid + anticancer drug
mixture ready to injectP ossibility of remixing, refill within closed
system (on-table mixing)

The mixture should be extemporaneously prepared and should be used
immediately after preparation

14-15

Bibliography

Features & benefits ofFeatures
Lipiodol®
Resistant& Unbreakable
Ergonomic& User-Friendly
Syringe back stop
Rotary finger grip
Optimized-handling

3W4P* Stopcock	SystemUnique 3-way		 4 Ports stopcock
Ports safe-guards
Closed system* 3-way & 4 ports

16-17

Benefits
24• Safety – No leak & no interaction content container• Swiftness – No devices break & no devices change

Device functionality verified
up to 24h in contact with Lipiodol®

(1)	Globocan 2012 Estimated Cancer Incidence, Mortality and Prevalence worldwide 2012.
(2)	EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. Journal of Hepatology 2012; 56: 908–943.
(3) Miyayama S. et al. Ultraselective Transcatheter Arterial Chemoembolization with a 2-F Tip Microcatheter for Small Hepatocellular Carcinomas: 		
Relationship Between Local Tumor Recurrence and Visualization of the Portal Vein with Iodized Oil. J Vasc Interv Radiol 2007; 18:365–376(4) Ikeda M. et al. Prospective study of transcatheter arterial chemoembolization for unresectable hepatocellularcarcinoma : an Asian cooperative study
between Japan and Korea. J. VAc. Interv. Radiol 2013;24: 490-500.
(5) Thierry de Baere et al., Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. Cardiovasc Intervent Radiol,
2016;39:334–343.

• Safety – No syringe pull-back & no liquids projection• Accuracy – Easy-to-handle & sharp• Swiftness – Easy-to-mix & easy-to-inject• Convenience – Ready-to-use• Efficacy – Homogeneous mixture• Safety – Reduced risks of infection, air injection, leaks• Swiftness – less connection mistakes& no disconnection time
• Convenience – On-table Mixing & optimized
injection control

LIPIODOL® ULTRA-FLUID. Composition: Ethyl esters of iodized fatty acids of poppy seed oil 10 mL, corresponding to an iodine content of 480 mg/mL. Indications(**): In diagnostic radiology - Hysterosalpingography - Ascending
urethrography – Lymphography – Sialography - Fistulography and exploration of abscesses - Exploration of frontal sinuses - Pre and post-operative cholangiography. In interventional radiology – Visualisation and localization (by selectiveintra-arterial use during CT) of liver lesions in adults with known or suspected hepatocellular carcinoma - Visualisation, localisation and vectorisation during Trans-Arterial Chemo-Embolisation (TACE) of hepatocellular carcinoma atintermediate stage, in adults – Selective embolization in combination with Histoacryl glue (particularly for arteriovenous malformation or aneurysms) – Selective injections of LIPIODOL® ULTRA-FLUID into the hepatic artery for diagnostic
purposes where a spiral CT scan is not practical. In endocrinology - Prevention of severe cases of iodine deficiency. Posology and method of administration (*): have to be adapted according to the type of examination, theterritories explored, the age and weight of the patient. The volume to be administered depends on the particular requirements of the technique and the size of the patient. Contraindications: Hypersensitivity to LIPIODOL® ULTRA-FLUID- Confirmed hyperthyroidism - Patients with traumatic injuries, recent haemorrage or bleeding – Hysterosalpingography during pregnancy or acute pelvic inflammation – Bronchography. In interventional radiology (Trans-Arterial ChemoEmbolization), Administration in liver areas with dilated bile ducts unless drainage has been performed. Special warnings and special precautions for use(*):There is a risk of hypersensitivity regardless of the dose administered.
Lymphography: Pulmonary embolism may occur immediately or after few hours to days from inadvertent systemic vascular injection or intravasation of LIPIODOL ULTRA-FLUID: Perform radiological monitoring during LIPIODOL® ULTRAFLUID injection and avoid use in patients with severely impaired lung function, cardiorespiratory failure or right-sided cardiac overload. Hypersensitivity: all iodinated contrast agents can lead to minor or major hypersensitivity reactions,which can be life-threatening. These hypersensitivity reactions are of an allergic nature (known as anaphylactic reactions if they are serious) or a non-allergic nature. They can be immediate (occurring within 60 min) or delayed (notoccurring until up to 7 days later). Anaphylactic reactions are immediate and can be fatal. They are dose-independent, can occur right from the first administration of the product, and are often unpredictable: avoid use in patients witha history of sensitivity to other iodinated contrast agents, bronchial asthma or allergic disorders because of an increased risk of a hypersensitivity reaction to LIPIODOL® ULTRA-FLUID. Thyroid: can cause hyperthyroidism in predisposed
patients. Lymphography saturates the thyroid with iodine for several months and thyroid exploration should be performed before radiological examination. Chemo-Embolization: Trans-Arterial Chemo-Embolisation is not recommendedin patients with decompensated liver cirrhosis (Child-Pugh ≥8), advanced liver dysfunction, macroscopic invasion and/or extra-hepatic spread of the tumour. Renal insufficiency must be prevented by correct rehydration before and after
the procedure. Oesophageal varices must be carefully monitored. Hepatic intra-arterial treatment can progressively cause an irreversible liver insufficiency in patients with serious liver malfunction and/or undergoing close multiple
sessions. The risk of superinfection in the treated area is normally prevented by administration of antibiotics. Embolization with glue: An early polymerisation reaction may exceptionally occur between LIPIODOL® ULTRA-FLUID andcertain surgical glues, or even certain batches of glue. Before using new batches of LIPIODOL® ULTRA-FLUID or surgical glue, the compatibility of LIPIODOL® ULTRA-FLUID and the glue must be tested in vitro. Interaction with othermedicinal products and other forms of interaction (*): Metformin, Beta blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, Diuretics, Interleukin II. Fertility, pregnancy
and lactation (*): LIPIODOL® ULTRA-FLUID must only be used in pregnant women if absolutely necessary and under strict medical supervision. Breastfeeding should be discontinued if LIPIODOL® ULTRA-FLUID must be used - Effects
on ability to drive and use machines: The effects on ability to drive and to use machines have not been investigated - Undesirable effects(*) most adverse effects are dose-related and dosage should therefore be kept as low
as possible :hypersensitivity, anaphylactic reaction, anaphylactoid reaction, vomiting, diarrhea, nausea, fever, pain, dyspnea, cough, hypothyroidism, hyperthyroidism, thyroiditis, pulmonary embolism, cerebral embolism, retinal veinthrombosis, lymphoedema aggravation, hepatic vein thrombosis, granuloma. Overdose (*) The total dose of LIPIODOL® ULTRA-FLUID administered must not exceed 20 mL - Pharmacodynamic properties (*) Pharmacotherapeuticgroup: X-ray contrast media, iodinated; ATC code: V08A D01.Water-insoluble iodinated contrast medium. Presentation (**) - 10 mL glass ampoule, box of 1 - 10 mL glass ampoule, box of 50. Marketing authorization holder(*): Guerbet - BP 57400 - F-95943 Roissy CdG cedex – FRANCE. Information: tel : 33 (0) 1 45 91 50 00. Revision: September 2, 2015.
(*) For complete information please refer to the local Summary of Product Characteristics(**) Indications, volumes and presentations may differ from country to country.
Reporting of suspected adverse reactions is important as it helps to continuously assess the benefit-risk balance. Therefore, Guerbet encourages you to report any adverse reactions to your health authorities or to our local Guerbet
representative.
Vectorio® is a medical device of Class Is (CE 0459) intended to be used by healthcare professionals only. Manufacturer: Medex, a Guerbet Group company. Intended use: Lipiodol® Resistant Mixing & Injection Systemfor conventional Trans-Arterial Chemo-Embolization (cTACE).
For complete information please refer to country’s local Package Information Leaflet & Vectorio® Instruction For Use (IFU).
Countries in which cTACE indication is registered: France, South Korea, Austria, Peru, Turkey, Hungary, Czech Republic, Mongolia, Argentina, The Netherlands, Vietnam, Mexico, Cambodia, New Zealand, Thailand, Taiwan & Brazil
For a copy of the SPC/ IFU, please contact a member of Guerbet.

18-19

24P17218 - November 2017 - Conception : Annapurna 8000 - Photos : Guerbet, Shutterstock.

Device functionality verified
up to 24h in contact with Lipiodol®

w w w. g u e r b e t . c o m