Vectorio efficacy & safety for improved cTACE...

Vectorio® efficacy & safety for improved cTACE mixing & delivery

cTACE Mixing & Injection System

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Device functionality verifiedup 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

p 3 Primary liver cancer epidemiology

p 4 Lipiodol® indication in HCC

p 5 BCLC staging system & treatment strategy

p 6 Dual arterial & venous perfusion for efficient cTACE

p 7 Overall survival data

p 8 Vectorio® intended use

p 9 Vectorio® Compounds

p 10 Vectorio® Set

p 14 Lipiodol® Ultra Fluid - anticancer drug mixture preparation using Vectorio®

p 16 Features & benefits of Vectorio®

p 17 Bibliography

2-3

782,000

554,000

228,000

Incidence746,000

95%

Mortality

out of 782,000 cases

Primary liver cancer epidemiology

• 782,000 new cancer cases worldwide occurred in 2012 (1)

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

• 2nd most common cause of death from cancer worldwide, 746,000 deaths in 2012 (1)

• HCC represents more than 90% of primary liver cancers (2)

• Very poor prognosis

PRIMARY LIVER CANCER - A DEADLY DISEASE

Lipiodol® indication in HCC

LIPIODOL® - INDICATED TO FIGHT HCC

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

• 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

Tumor necrosis & size reduction

Cancerous tumor

Embolic material

Cancerous tumor

Catheter

Lipiodol® + anticancer drug

4-5

Tumor

Liver

Iliac artery

Hepatic artery

Aorta

Micro-catheter

BCLC staging system & treatment strategy (2)

HCC

Stage A-CStage 0

Very early stage (0) Early stage (A)

Single

Portal pressure/bilirubin

Increased

Normal

Resection RF/PEI TACE Sorafenib Best supportive careLiver transplantation(CLT/LDLT)

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

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

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

Target: 10%OS: < 3 mo

No Yes

3 nodules ≤ 3 cm

Associated diseases

Intermediate stage (B) Advanced stage (C) Terminal stage (D)

Stage D

PST 0-2, Child-Pugh A-BPST 0, Child-Pugh A

Single < 2 cm,Carcinoma in situ

Single or 3 nodules ≤ 3 cm, PS 0 Multinodular, PS 0 Portal invasion,N1, M1, PS 1-2

PST >2, Child-Pugh C*

cTACE: "STANDARD-OF-CARE" FOR STAGE B HCC PATIENTS

bClC = barcelona-Clinic liver Cancer

Vectorio®

Dual arterial & venous perfusion for efficient cTACE (3)

6-7

PERIBILIARY PLEXA ALLOW LIPIODOL®-DRUG DROPLETS SHUNTING FROM HEPATIC ARTERY TO PORTAL VEIN

HCC

Catheter

Grade 0 Grade 1 Grade 2

Arterial enhancementof the tumor

Early venous enhancementthanks to the peribiliary vascular plexa

Full visualization of thearterioportal vascular bed

Catheter Catheter

HCC HCC

Grades of portal vein visualization & size of tumors treated with ultraselective cTACE

• Radiological evidence of dual vascularization of HCC

Grade 0 Grade 1Grade 2

Overall survival data (2, 4)

SIGNIFICANT IMPROVEMENT OF STAGE B HCC PATIENT OVERALL SURVIVAL

16 months

3745 months

20 months

8-9

intented use

Anticancer drugs that may be associated with LipiodoL® Ultra Fluid***

Cisplatin Doxorubicin Epirubicin Mitomycin

* Guerbet project under progress

A

B

C

D

E

F

G

H

I

compounds

A & B 20 mL mixing syringes (x2)C Particle filter for Lipiodol® Ultra Fluid withdrawal (x1)D Lipiodol® Ultra Fluid ampoule withdrawing straw (x1)E *Lipiodol® Ultra Fluid vial spike (x1)F 3-way stopcock with 4 connections (x1)G Connector (x1)H 1 mL injection syringe (x1)I 3 mL injection syringe (x1)

The system does not contain:• Lipiodol® Ultra Fluid ampule or vial• Anticancer drug• Microcatheter

Mixture preparation recommendations**

Lipiodol® Ultra Fluid - anticancer mixture should be performed with *

Lipiodol® Ultra Fluid may be associated with various anticancer drugs

• 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

• Vigorous mixing of Lipiodol® & anticancer drug via the stopcock

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LipiodoL® Resistant Mixing & Injection System for conventional Trans-Arterial Chemo-Embolization (cTACE)

*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

Raw materials of Vectorio® have been validated for resistance to Lipiodol® up to 24h

10-11

Set

Mixing syringes (20 mL)Design Aim - Making multiple mixes easy & safe

plunger -- Ergonomic convex shape, rotatable, atraumatic for the palm & fingers

backstop (patented) -- Prevents accidental release & uncontrolled drug exposure

rotary finger support -- Adjustable working position after connection

• O-ring design -- Sealing function • Elimination of the elastic zone -- Tactile feedback improvement, direct transmission of forces from hand to mixture

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Injection syringe (1 mL & 3 mL)Design Aim - Making injection easy & safe

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plunger -- Ergonomic design for optimal grip and easy injection

backstop (patented) -- Prevents accidental release & uncontrolled drug exposure

rotary finger support -- Obtain more suitable working position

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

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

raw materials - Strong & Resistant for cTACE use

• Connects 2 mixing syringes, Injection syringe & catheter

• The "L" channel & Rotary handle enable to chose which two ports can be connected

Mix, inject, refill or remixno need to disconnect

Foolproof Luer lock connection

• Vectorio� mixing syringes can't be connected to injection port

• Mixing ports can't communicate with the patient

Catheter/patient line connection

Injection portMixing ports

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24


12-13

Double female connector

Design Aim - Easy & safe to perform preparation

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Transfer drug from the pharmaceutical preparation syringe to the mixing syringe

of Vectorio®

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

Particle filter for withdrawing Lipiodol®

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Lipiodol® Ultra Fluid - anticancer drug mixture preparation using

1 dRug vOlumE

2 lipiOdOl® vOlumES 5

TO

STEP I: Withdrawing STEP II: Mixing STEP III: Injecting

Withdraw Lipiodol® Ultra Fluid and anticancer drug into the 2 mixing syringes

Perform 20 vigorous back & forth movements to obtain an homogeneous mixture 5

Lipiodol® Ultra Fluid + anticancer drug mixture ready to inject

Connect stopcock to the microcatheter

Connect the mixing syringes to the 4 ports 3 way stopcock

Anticancer drug should be first pushed towards the syringe containing Lipiodol® 5

Possibility of remixing, refill within closed system (on-table mixing)

THE MIXTURE SHOULD BE EXTEMPORANEOUSLY PREPARED AND SHOULD BE USED IMMEDIATELY AFTER PREPARATION

1st

(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.

16-17

Features & benefits of Bibliography

Features Benefits

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

• 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

3W4p* stopcock system

Unique 3-way 4 Ports stopcock

Ports safe-guards Closed system

lipiodol® resistant

& Unbreakable

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* 3-way & 4 ports

ergonomic & User-Friendly

Syringe back stop Rotary finger grip Optimized-handling

• Safety – No syringe pull-back & no liquids projection• Accuracy – Easy-to-handle & sharp• Swiftness – Easy-to-mix & easy-to-inject• Convenience – Ready-to-use

18-19

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 selective intra-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 at intermediate 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, the territories 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 Chemo-Embolization), 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® ULTRA-FLUID 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 (not occurring 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 with a 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 recommended in 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 and certain 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 other medicinal 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 vein thrombosis, lymphoedema aggravation, hepatic vein thrombosis, granuloma. Overdose (*) The total dose of LIPIODOL® ULTRA-FLUID administered must not exceed 20 mL - pharmacodynamic properties (*) Pharmacotherapeutic group: 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 system for 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 & BrazilFor a copy of the SPC/ IFU, please contact a member of Guerbet.

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Vectorio efficacy & safety for improved cTACE...

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