GEST Training Presentation

Not for Distribution to HCPs
DC Bead Marketing Messages

TM
and Objection Handling
Biocompatibles UK Ltd is a
BTG International group company
Disclaimer
• DC Bead™ is CE marked and is indicated for the treatment of malignant hypervascular tumours
and loading with doxorubicin drug. DC Bead™ is also indicated for loading with irinotecan for the
treatment of metastatic colorectal cancer.
• DC BeadM1™ is primarily intended as an embolic agent for the treatment of malignant
hypervascularised tumour(s). DC BeadM1™ is compatible with irinotecan, which can be loaded
prior to embolisation and then, as a secondary action, elute a local, controlled and sustained
dose to the mCRC after embolisation. DC BeadM1™ is compatible with doxorubicin, which can
be loaded prior to embolisation and then, as a secondary action, elute a local, controlled and
sustained dose to the tumour after embolisation.
• Both products and/or all indications may not be available in your territory. DC Bead™ is
not cleared by the FDA for sale or distribution in the USA.
• Copies of this presentation and any supporting material are confidential and are for internal,
educational purposes only, and must not be used or distributed in the field
• Although the information in this presentation has been produced and processed from sources
believed to be reliable, no warranty express or implied is made or assumed regarding accuracy,
adequacy, completeness, legality or reliability of any such information, and any and all such
warranties are expressly disclaimed
• DC Bead, DC BeadM1, DEBIRI and DEBDOX are trademarks and/or registered trademarks of
Biocompatibles UK Limited. Biocompatibles UK Ltd is a BTG International group company. BTG
and the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks
in the USA, the European Union and certain other territories. Copyright © 2013, Biocompatibles
UK Ltd.
2
DC Bead, DC BeadM1, DEBIRI and DEBDOX are trademarks and/or registered trademarks of Biocompatibles UK Limited. Biocompatibles UK Ltd is a BTG International group
company. BTG and the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in the USA, the European Union and certain other territories.
Copyright © 2013, Biocompatibles UK Ltd. GxUS-DCB-2013-0033
DC Bead™ and DC BeadM1™

Safety Information
DC Bead™ and DC BeadM1™ Important Safety Information:

Cautions: DC Bead and DC BeadM1: Embolisation with DC Bead and DC BeadM1 should only be performed by a physician
with appropriate interventional occlusion training in the region intended to be embolised. Do not use if the vial or packaging
appear damaged. Ensure that DC Bead/DC BeadM1 is an appropriate size for the intended vasculature. Consider upsizing to a
larger size of DC Bead in the presence of AV shunts or if angiographic evidence of embolisation does not appear quickly during
delivery. Consideration should be given to Tc99m-MAA scanning if there is suspicion of AV shunting.
Cautions: Irinotecan-loaded DC Bead/DC BeadM1: On addition of non-ionic contrast/water mixture to irinotecan-loaded
beads, some irinotecan will be eluted over time. If the beads are not used immediately, up to 10mg irinotecan may be present in
the contrast/water mixture. If this occurs, a small dose of irinotecan may be available systemically at time of delivery. Do not
use irinotecan-loaded beads with contrast agents containing salts (e.g. Calcium chloride). The maximum amount of irinotecan
that can be loaded is 100mg irinotecan per 2ml vial of DC Bead/ DC BeadM1. Exceeding this amount may lead to some
irinotecan remaining free in solution. This free solution should be removed prior to use to prevent the patient receiving the
excess dose as a bolus.
Cautions: Doxorubicin-loaded DC Bead/DC BeadM1: Exceeding a loading dose of 37.5mg doxorubicin per 1ml DC Bead/
DC BeadM1 may lead to some systemic distribution of doxorubicin and related side effects.
Potential Complications: DC Bead/DC BeadM1: Undesirable reflux or passage of DC Bead/DC BeadM1 into normal arteries
adjacent to the targeted lesion or through the lesion into other arteries or arterial beds. Non-target embolisation. Pulmonary
embolisation. Ischaemia at an undesirable location. Capillary bed saturation and tissue damage. Ischaemic stroke or ischaemic
infarction. Vessel or lesion rupture and haemorrhage. Neurological deficits including cranial nerve palsies. Vasospasm. Death.
Recanalisation. Foreign body reactions necessitating medical intervention. Infection necessitating medical intervention. Clot
formation at the tip of the catheter and subsequent dislodgement causing arterial thromboembolic sequelae.
3
DC Bead, DC BeadM1, DEBIRI and DEBDOX are trademarks and/or registered trademarks of Biocompatibles UK Limited. Biocompatibles UK Ltd is a BTG International group company. BTG and
the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in the USA, the European Union and certain other territories. Copyright © 2013, Biocompatibles UK
Ltd. GxUS-DCB-2013-0033
DC BeadTM – Objectives
ProductDC Bead TM
Indications
HCC mCRC
Establish market for

Protect and grow DC BeadTM for treatment
Objectives
DC Bead TM
share of of metastatic liver
HCC market tumours
4
DC BeadTM in HCC
Protect and grow

Objective DC BeadTM share of HCC
market
DC Bead™, the only clinically proven drug-

Positioning
eluting bead, delivers the gold-standard
treatment in intermediate HCC
Continue to Protect market

expand into Increase
early and late Strategies DC BeadTM use share
DC BeadTM vs
segments of vs. cTACE
Competitors
BCLC
5
DC BeadTM vs cTACE: Messaging

“The Evidence is Clear”
• Improved tolerability1,2,
• Protect healthy liver1
• Proven response rates1,2,3, 4
• Standardised technique5
• Significantly improved response rate in
more advanced patients1,3
• Improved survival6,7
• CE mark approved for loading
PUBLICATION JOURNAL CLUB CLINICAL SUMMARY CLINICAL SERIES INSERT
1. Lammer et al. 2010 : PRECISION V ✔ ✔ ✔
2. Varela et al. 2007: Efficacy and PK data ✔ ✔ ✔
3. Song et al. 2011: DC BeadTM vs cTACE ✔ ✔ ✔
4. Dhanaskaran et al. 2010: DC BeadTM vs cTACE ✔ ✔ ✔
5. Lencioni et al. 2010: Technical recommendations

6. Burrel et al. 2012: Four-year survival ✔ ✔ ✔
7. Malagari et al. 2012: Five-year survival ✔ ✔
6
DC BeadTM vs cTACE: Materials
DC BeadTM vs. cTACE sales presentation

Clinical series in HCC
Stability folder
Lencioni et al. Technique Guidelines
7
DC BeadTM vs Competition: Messaging
“The Evidence is Clear”

• Improved tolerability “More than just a product”
• Protect healthy liver Benefits of buying a premium
• Proven response rates product from a market leader
• Significantly improved response • Knowledgeable sales force
rate in more advanced patients • Distributors with quality image /
• Improved survival reputation and relationships
• Standardised technique • Physicians education programme
• CE mark approved for loading (training – workshops – centres of
See slide 6 for references excellence etc.)
• Continued leadership in product
development, clinical research and
“All products are not publications
the same”
“Hands off our data!” All
8
DC BeadTM vs Competition: Materials
“Evidence is clear” pack

DC BeadM1 brochures
Stability data brochure
9
DC BeadTM in Early and Late Stages:

Messaging
“The Evidence is Clear” “The Evidence is clear”

• Improved tolerability
• Protect healthy liver
• Proven response rates Proven and sustained response
• Significantly improved response rates in multiple patient segments
rate in more advanced patients - Pre-transplant2,3,4
• Improved survival - Advanced patients1,5
• Standardised technique - With Sorafenib1
• CE mark approved for loading
See slide 6 for references
PUBLICATION JOURNAL CLUB CLINICAL SUMMARY CLINICAL SERIES INSERT
1. Pawlik et al. 2011: DC beadTM + Sorafenib ✔ ✔ ✔
2. Nicolini et al. 2010: DC beadTM prior transplantation ✔ ✔
4. Aloia et al. 2007: Interval of efficacy for TACE prior transplant

5. Lammer et al. 2010: Precision V ✔ ✔ ✔
10
DC BeadTM in Early and Late Stages:

Materials

Hepatology brochure
Working on pre-transplant strategy
11
Messaging to Pharmacist
Storage time of 14 days when loaded

with doxorubicin and 7 days when mixed
with contrast medium2
CE Mark for loading Reproducible and

with doxorubin homogeneous drug loading
and elution1
Peer-review published
storage stability data2
PUBLICATION
1. Jordan et al. 2010: DC BeadTM vs HepaSphere

2. Hecq et al. 2012: DC BeadTM stability data
12
Materials for Pharmacist
Coming
soon!

Loading instructions (brochures and videos)
Future pharmacy guide
13
DC BeadTM in mCRC
Establish market for

Objective DC BeadTM for treatment of
metastatic liver tumours
DEBIRI™ is a well-tolerated liver-directed therapy that
Positioning
complements current treatment strategies, with potential
benefits in terms of access to curative therapies, response, quality
of life and survival
Target Leverage Build solid
HCPs
Strategies
referring relationship with referral base to
drive advocacy
IR community
14
Messaging to Medical Oncologist
DEBIRITM with DC BeadTM may give certain DEBIRITM with DC BeadTM

patients more treatment options has been shown to have
potential to:
• Downstage patients to
potentially curative therapies1
• Improve response and survival
DEBIRITM with DC BeadTM DEBIRITM with DC BeadTM
vs systemic therapies alone4
Clinical trials: can be used with current • Improve quality of life –
• Initial results are promising 1, 2, 3,4 therapies in multiple increased dose with fewer AEs
• On-going clinical programme patient segments1,2,3 and no dose-limiting toxicity4
Note: Speak to reference centre/medical team before starting a programme!

PUBLICATION JOURNAL CLUB CLINICAL SUMMARY
1. Martin et al. 2012: Concomitant with systemic therapy (1 –line) st ✔
All ✔
2. Martin et al. 2011: Concomitant with systemic therapy (2nd–line) ✔ ✔
3. Martin et al. 2009: Concomitant with systemic therapy (2nd–line) ✔
4. Fiorentini et al. 2012: Salvage therapy ✔ ✔
15
Materials for Medical Oncologist
DEBIRITM medical oncology brochure

Pain management information
Multi-disciplinary team DEBIRITM
presentation
16
Messaging to Surgical Oncologist
DEBIRITM with DC BeadTM as DEBIRITM with DC BeadTM DEBIRITM with DC BeadTM

a neoadjuvant therapy has been shown to have Clinical trials:
• Initial results are promising1,2, 3,4,5
prior to resection may potential to: • On going clinical programme
offer: • Downstage patients to
• Reduced morbidity at surgical therapies1,2
resection vs systemic
chemotherapy2,3,4,5
• Improved response in target
tissue3
• Protection of healthy liver2,3,4,5

1. Martin et al. 2012: Concomitant with systemic therapy (1st –line) ✔ ✔
2. Bower et al. 2011: Downstaging unresectable patients ✔
3. Poston G. Presentation IHPBA Paris 2012: Neoadjuvant prior to resection

4. Jones RP et al. 2012: Neoadjuvant prior to resection
5. Blazer DG et al. 2008: Pathological response after FOLFOX/FOLFIRI
17
Materials for Surgical Oncologist
DEBIRITM surgical oncology brochure

Multi-disciplinary team DEBIRITM
presentation
18
Messaging to Interventional Radiologist
There are important differences with The only product CE mark approved
DEBIRITM vs TACE for HCC – make for loading with irinotecan
sure you know what they are
DEBIRITM with DC BeadTM may give certain

patients more treatment options

1. Martin et al. 2012: Concomitant with systemic therapy (1st –line) ✔ ✔
2. Bower et al. 2011: Downstaging unresectable patients ✔
3. Poston G. Presentation IHPBA Paris 2012: Neoadjuvant prior to resection

4. Jones RP et al. 2012: Neoadjuvant prior to resection
5. Fiorentini et al. 2012: Salvage therapy ✔ ✔
19
DC Bead, DC BeadM1, DEBIRI and DEBDOX are trademarks and/or registered trademarks of Biocompatibles UK Limited. Biocompatibles UK Ltd is a BTG International group company. BTG and the
BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in the USA, the European Union and certain other territories. Copyright © 2013, Biocompatibles UK Ltd. GxUS-
DCB-2013-0033
Materials for Interventional Radiologist
Coming
soon!
DEBIRITM brochure
Pain management information
Multidisciplinary DEBIRITM presentation
20
Objections
Management
Objections handling steps
Listen to the Objection

Don't jump all over the prospect as soon as he says “But what about-.” Give him a chance to explain exactly what's bothering him.
Say it Back to the Prospect

This both shows that you were listening and gives him a chance to clarify.
Explore
Sometimes the first objections aren't the prospect's the Reasoning
real concern. Before you launch into answering an objection, ask some
questions.
If you have specific examples, such as a story fromAnswer the

an existing Objection
customer or data - present them – hard facts make your response
stronger.
Check
Take a moment to confirm that you've answered the Back withobjection
prospect's the Prospect
fully. Usually this is as simple as saying, "Does that
make sense?”
Redirect the Conversation

Bring the prospect back into the flow of the appointment.
22
Objections handling tips
Replace “but” with the word “and”

The word "and" conveys a partnership message rather than a pending argument.
"And why do you say that (or feel that way)?”
Keep the prospect speaking

Always keep the prospect speaking and avoid questions leading to a Yes/No answer. The
more the prospect talks the more is learned about their problems. Knowing the
customer needs makes it easier to customise the sales message.
Keep the dialogue alive

Keep the dialogue alive with the "obviously you" technique to stay on track. This
technique works especially well with emotional objections. Listen for emotional signs
which include always, never, every time. Then respond with "Obviously you have a
reason for saying that. Do you mind if I ask what that is?"
23
HCC Objections (6)
DEBDOXTM has failed to show superiority versus

bland embolisation (K Brown poster ASCO GI)
Abstract:
• Patients (pts) with unresectable Okuda stage I or II HCC with adequate liver function
were randomized to Bead Block or LC Bead loaded with 150 mg of doxorubicin.
• Pts were evaluated by multiphasic CT 2-3 weeks post-treatment. Progression by
RECIST and/or evidence of ≤5% necrosis was considered treatment failure.
• Results: 101 pts were randomized, 51 to Bead Block and 50 to LC Bead. Demographics
in the two groups were comparable: median age was 67, 77% were male and 81% were
Okuda I.
• Median number of embolizations was 2 in both arms.
• There was no difference in adverse events. There was no difference in RR: Bead Block
11% vs LC Bead 9% (p=0.58). Median TTP was not reached. 12 month TTP was 49
versus 56% (p=0.84), median PFS was 7 versus 9 (p=0.6), and OS 14 versus 16 months
(p=0.7) for Bead Block and LC Bead respectively. Change in TN/tumor volume post
treatment did not predict OS in either group (p=0.28).
• Conclusions: No difference in response was noted between pts treated with Bead Block
versus LC Bead. Given the comparable safety profile, TTP, PFS and OS, HAE should be
considered a reasonable and cost-effective therapeutic option and may be preferable to
LC Bead. Clinical trial information: http://clinicaltrials.gov/show/NCT00539643
25

Rebuttal points:
• Results are not published yet and have been presented on a poster only
• Study is not powered to detect a difference between the two groups. It cannot show
equivalence or non-inferiority
• It was a single center study that involved a group of sicker patients
• This centre (Memorial Sloan Kettering) has a very specific technique, including giving
patients general anaesthesia – they work outside the technical recommendations
for DEBDOXTM with DC Bead™
• The primary endpoint was tumour response by RECIST at 2-3 weeks after the
single initial treatment
• Most studies evaluate 6-month response after multiple treatments
• Trends in favour of DEBDOXTM were observed in overall survival
• The outcome varies from other recent publications (Malagari 2010, Malagari 2012,
Burrell 2012)
26

Data from K Brown poster is not consistent with current peer reviewed publications
27
DEBDOXTM has failed to show superiority

versus conventional TACE (SACCO’s paper)
Abstract:
Patients with unresectable HCC unsuitable for ablative therapies were randomly
assigned to undergo conventional or DEB chemoembolization. The primary endpoints of
the study were safety, toxicity, and tumor response at 1 month.
Results: 67 patients (mean age, 70 y 7.7) were evaluated. Mean follow-up was 816
days 361.
Two periprocedural major complications occurred (2.9%) that were treated by medical
therapy without the need for other interventions. A significant increase in alanine
aminotransferase levels 24 hours after treatment was reported, which was significantly
greater after conventional chemoembolization (n34) than after DEB chemoembolization
(n33; preprocedure, 60 IU44 vs 74 IU62, respectively; at 24 h, 216 IU201 vs 101 IU89,
respectively; P0.007). No other differences were observed in liver toxicity between
groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%,
respectively, in the conventional chemoembolization group and 51.5% and 48.5%,
respectively, in the DEB chemoembolization group. No differences were observed
between groups in time to recurrence and local recurrence, radiologic progression, and
survival.
Conclusions: Conventional chemoembolization and DEB chemoembolization have a
limited impact on liver function on short- and long-term follow-up and are associated with
favorable clinical outcomes. 28

Rebuttal points:
• Study objective unclear - designed for equivalence, non-inferiority, two-tailed
superiority or just descriptive.
• The primary endpoints of the study were safety, toxicity, and tumour response at 1
month. Response was assessed after the 1st procedure only.
• Most studies including Precision V (PV) evaluate 6-month response after multiple
treatments
• Patients may have received more than one chemoembolisation and no data
provided on patients responding later.
• The mean doxorubicin dose received by the patients in both groups is low (around
55mg) and other studies have shown good results using DC Bead TM with similar dose
(Song et al. 2011)
• The technical recommendation for intermediate HCC is to use 150mg per treatment.
• Significant difference in the ALT levels between the cTACE group and DEBDOX TM
(p=0.007). This supports findings from Precision V that DEBDOX TM “protects healthy
liver”.
29

Other data confound data from SACCO
Song et al:
• Patients in the DEBDOX™ group received a
maximum dose of 2ml of DC Bead™ loaded
with 50mg of doxorubicin
• The treatment response in the DC Bead™
group was significantly higher than that of the
cTACE group (P<0.001)
• The time to progression was significantly better
in the DC Bead™ group than in the cTACE
group (11.7 and 7.6 months, respectively,
P=0.018)
• Subgroup analysis showed that, in intermediate-
stage HCC, DC Bead™ treatment resulted in a
significantly better treatment response and
longer time to progression than cTACE
(P<0.001 and 0.038, respectively)
30
Doxorubicin is not indicated for the

treatment of HCC
• Ask the physician what drug he currently uses? We are not aware of
any drug approved for HCC specifically
• Doxorubicin is not indicated in HCC and as you may know it is
approved for the treatment of solid tumours and for intra-arterial
administration. HCC is a solid tumour
• The IFU states that DC BeadTM are intended to be loaded with
doxorubicin for the purpose of embolisation of vessels supplying
malignant hypervascularised tumour. HCC is a hypervascularised
tumour
31
Radioembolisation has superior results to

DEBDOXTM
• Ask the physician what evidence leads him to this claim – we are
not aware of a comparative study
• The only way to draw this conclusion would be based on
randomised controlled studies comparing DEBDOXTM vs
radioembolisation
32
Multifocal disease is widely seen – how should

DEBDOXTM be used in this presentation?
• The most appropriate approach has to be decided in a

multidisciplinary team
• Guidelines include recommendation on lobar approach:
– The catheter should be placed as selectively as possible in the right or left
hepatic artery, identify the origin of the cystic artery as well as other arteries
supplying flow to extrahepatic organs. If identified, these vessels must be either
embolised using coils or avoided by placing the catheter tip well beyond the
origin of these vessels
• There are several studies including patients with multifocal disease
for instance:
– M Varela et al. - Journal of Hepatology 2007; 474–481
– RT Poon et al. - Clin Gastroenterol and Hepatol 2007;5:1100-1108
33
Liver disease seen in the UK is different from the rest of Europe and
therefore would not necessarily follow the guidelines offered.
• It refers mainly to the underlying cause of the cirrhosis and whereas mainland
Europe sees hepatitis as the main cause in the UK it tends to be alcohol
related
• The actual disease they see is different with a lot more multifocal disease
which sometimes makes it difficult to take a super selective approach
• Ask the physician what treatment he currently uses
• There are several studies including patients with multifocal disease
with for instance:
– M Varela et al. - Journal of Hepatology 2007; 474–481
– RT Poon et al. - Clin Gastroenterol and Hepatol 2007;5:1100-1108
• In the papers published there is no subgroup analysis looking into
Hepatitis C vs. alcoholic patients
• TACE II study is currently on-going in the UK and might give us further
insights
34
mCRC Objections (8)
DEBIRITM has similar results to conventional

TACE in mCRC
• Ask the physician if he is referring to a specific publication showing

these results. Also check where the information is coming from.
• DEBIRITM with DC BeadTM is a treatment option for these patients
which is not comparable with cTACE with irinotecan
• We currently have a number of DEBIRITM publications that we can
discuss further
• Standardised guidelines on the use of DEBIRITM in mCRC are in
print
36
Which patients are suitable

candidates for DEBIRITM?
These notes are for guidance only and should not be seen as a recommendation or used in isolation to
make clinical decisions that relate to patient care or medication.
Eligibility for DEBIRITM treatment should be established in each individual case by a multidisciplinary
team.
Potential candidates for DEBIRITM treatment
• Unresectable liver metastases of colorectal cancer. In case of resectability, consider
neoadjuvant DEBIRITM treatment.
• Liver dominant disease: ≥ 80% disease located in the liver
• Liver involvement/replacement ≤ 60%
• Adequate liver function:
 Serum transaminases
(AST & ALT) < 5 x ULN*
 Bilirubin ≤ 2mg/dL
• Adequate haematological and renal function:
• ANC** ≥ 1500/mm3,
Platelets ≥ 100 000/mm3
• Creatinine clearance ≥ 60 mL/min
• PS= 0-1
* ULN: Upper Limit of Normal; ** ANC: absolute neutrophil count
37
the BTG roundel logo are trademarks of BTG International Ltd and are registered trademarks in the USA, the European Union and certain other territories. Copyright © 2013, Biocompatibles UK Ltd.
GxUS-DCB-2013-0033
Which patients are suitable candidates for

DEBIRITM?
Contraindications
• Known hypersensitivity to irinotecan
• Chemoembolisation (TACE) is contraindicated in the following:
– Patients intolerant to occlusion procedures
– Vascular anatomy or blood flow that precludes catheter placement or embolic injection
– Presence of large porto-systemic shunt
– Hepatofugal blood flow
– Main portal vein thrombosis
– Presence or likely onset of vasospasm
– Presence or likely onset of haemorrhage
– Presence of severe atheromatous disease
– Presence of feeding arteries smaller than the distal branches from which they emerge
– Presence of patent extra-to-intracranial anastomoses or shunts
– Presence of collateral vessel pathways potentially endangering normal territories during embolisation
– Presence of arteries supplying the lesion not large enough to accept DC Bead TM
– Vascular resistance peripheral to the feeding arteries precluding passage of DC Bead TM into the lesion
38
There is a lack of clinical evidence for

DEBIRITM in mCRC
• Yes the clinical evidence on DEBIRITM is limited and there is an on-

going clinical programme to build this evidence
• Based on the available data, which patients do you think might be

suitable for this treatment?
• Would you consider recruiting patients in a DEBIRITM study?
• The current DEBIRITM clinical results are as follows…
Note: Speak to reference centre/medical team before starting a programme

39

DEBIRITM in mCRC (cont’d)
Results of Biocompatibles sponsored

PARAGON II study: Feasibility of
Neoadjuvant DEBIRI™ with DC Bead™ for
Resectable Liver Metastases
DEBIRI™ with DC Bead™ may offer:

– Improved response in target tissue
– Protection of healthy liver due to
targeted nature of drug delivery
– Reduced risk of excessive bleeding due
to sinusoidal congestion and thrombosis
(systemic oxaliplatin)
– Reduced risk of steatosis and
steatohepatitis (systemic irinotecan),
which can lead to post-operative liver
failure and 90-day death
40

DEBIRI in mCRC (cont’d)
Results of Fiorentini’s study: Intra-arterial

Infusion of Irinotecan-loaded Drug-eluting Beads
(DEBIRI™) versus Intravenous Therapy
(FOLFIRI) for Hepatic Metastases from Colorectal
Cancer: Final Results of a Phase III Study
– Overall survival: DEBIRI™ demonstrated
significant improvement compared to FOLFIRI
(p = 0.031)
– Progression-free survival: DEBIRI™
demonstrated significant improvement (p =
0.006) compared to FOLFIRI
– Response: 24 patients (68.6%) in the
DEBIRI™ group had liver-specific objective
response versus 7 patients (20%) in the
FOLFIRI group. Progressive disease was
observed in 7 patients (20%) in the DEBIRI™
group vs 16 (45.7%) in the FOLFIRI group
– Quality of life: DEBIRI™ patients
demonstrated significantly better physical
functioning at 1 month 3 months and 8 months
than FOLFIRI patients
41

The clinical evidence obtained so far is the rationale of the three

investigator sponsored studies currently on-going associating DEBIRITM
with different chemotherapy in the first line treatment of mCRC:
PHASE II: Drug-Eluting Bead, Irinotecan (DEBIRITM) Therapy of Liver Metastasis From Colon
Cancer With Systemic FOLFOX6
• Principal Investigator: Robert C.G. Martin, Sponsor: University of Louisville
• The study compares 2 treatment arms:
– Experimental: DEBIRITMwith FOLFOX6 + Avastin
– Active Comparator: FOLFOX6/Avastin alone
• Number of patients: 70
• Data expected to be available in 2013

42

PHASE II: Chemoembolisation With CPT11 Loaded DC BeadTM With Cetuximab and 5FU/LV in
First Line in Patients With KRAS Wildtype mCRC
• Principal Investigator: Prof. Dr. Eric Van Cutsem, Universitaire Ziekenhuizen Leuven
• Primary Outcome Measures:
– Feasibility of chemoembolization with DC Bead TM loaded with Irinotecan
– Feasibility of the study by measuring the number of enrolled patients who can finish the first
cycle of treatment
• Estimated Enrolment: 20 patients
• Estimated study completion date: October 2014
Phase II: Intra-arterial hepatic beads loaded with irinotecan (DEBIRI TM) with concomitant
chemotherapy with FOLFOX in patients with colorectal cancer with unresectable liver
metastases: a phase II multicenter study.
• Principal investigator: Prof. Julien Taieb, Hôpital Européen Georges Pompidou, Paris. Sponsor:
FFCD, 10 Centres
• Primary Outcome Measures: Progression-free survival rate at 9 months
• Estimated enrolment: 58 patients
• Estimated first patient: Q2 2013
43
DEBIRITM does not have good results in

mCRC
• Yes, some centres had some disappointing results and we are currently
developing the technique. Technical guidelines are currently in print
• We believe there are some patient groups who would benefit from DEBIRITM
with DC BeadTM
• These results have been considered strong enough by top groups in the
field to justify the conduct of the studies they are sponsoring in first line
treatment of mCRC
• Ask the oncologist about his current practice about the results obtained with
other options
• The use of DEBIRITM in patients having received more than two lines of
chemotherapy is supported by Fiorentini´s data and single centre
experiences reported

44
DEBIRITM results in third-line patients are

disappointing
• Yes some centres got some disappointing results and we are currently
developing the technique. Technical guidelines are currently in print
• We believe there are some patient groups who would benefit from DEBIRITM
with DC BeadTM
• These results have been considered strong enough by top groups in the
field to justify the conduct of the studies they are sponsoring in first line
treatment of mCRC
• Ask the oncologist on his/her current practice about the results obtained
with other options
• The use of DEBIRITM in patients having received more than two lines of
chemotherapy is supported by Fiorentini´s data and single centre
experiences reported

45
DEBIRITM is Painful for the Patient
• While DEBDOXTM is a well established

treatment option, DEBIRITM is a different
treatment which requires a specific pain
management protocol
• It is important to manage physicians’
expectations before starting a
programme
• If DEBIRITM is already used in this centre,
ask the physician about his/her current
practice about the pain management
protocol used with DEBIRITM
• Pain can be managed and several pain
management protocols have been
described by different groups (Eg
Aliberti / Martin pain management)

46
Do we always need to stop systemic chemotherapy

when using DEBIRITM with DC BeadTM?
• Studies assessing the feasibility of DEBIRITM

associated to chemotherapy are on-going.
– Dr Robert Martin phase 1 study showed positive
pharmacokinetics results using DEBIRI™ in
Treatment of Chemo-Naïve Unresectable
mCRC with Concomitant Systemic Fluorouracil
and Oxaliplatin [FOLFOX]. The phase II study is
currently on-going
– Another phase II study is looking at
Chemoembolisation With CPT11 Loaded
DC BeadTM With Cetuximab and 5FU/LV in First
Line in Patients With KRAS Wildtype mCRC
• The objective is to use DEBIRITM in
combination with chemotherapy if appropriate
• Many physicians take the advantage from
DEBIRITM during chemoembolisation break or
"chemo-holiday" to offer DEBIRI
47
Irinotecan cannot be administrated intra-

arterially
• Irinotecan Solution is intended for intravenous use and in all cases

the instructions for use are referring to the intravenous
administration
• There is no contraindication in the Irinotecan Summary Product
Characteristics for intra-arterial use
• This is related to Irinotecan Solution, and DEBIRITM is a different
treatment
• The IFU states that DC BeadTM are intended to be loaded with
irinotecan for the purpose of: Embolisation of vessels supplying
malignant colorectal cancer metastasised to the liver, indicating that
this is an accepted use
48

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DC Bead Marketing Messages

and Objection Handling

DC Bead™ and DC BeadM1™

DC Bead™ and DC BeadM1™ Important Safety Information:

Establish market for

Protect and grow

DC Bead™, the only clinically proven drug-

Continue to Protect market

DC BeadTM vs cTACE: Messaging

PUBLICATION JOURNAL CLUB CLINICAL SUMMARY CLINICAL SERIES INSERT

1. Lammer et al. 2010 : PRECISION V ✔ ✔ ✔

2. Varela et al. 2007: Efficacy and PK data ✔ ✔ ✔

3. Song et al. 2011: DC BeadTM vs cTACE ✔ ✔ ✔

4. Dhanaskaran et al. 2010: DC BeadTM vs cTACE ✔ ✔ ✔

5. Lencioni et al. 2010: Technical recommendations

7. Malagari et al. 2012: Five-year survival ✔ ✔

DC BeadTM vs cTACE: Materials

DC BeadTM vs. cTACE sales presentation

DC BeadTM vs Competition: Messaging

“The Evidence is Clear”

DC BeadTM vs Competition: Materials

“Evidence is clear” pack

DC BeadTM in Early and Late Stages:

“The Evidence is Clear” “The Evidence is clear”

PUBLICATION JOURNAL CLUB CLINICAL SUMMARY CLINICAL SERIES INSERT

1. Pawlik et al. 2011: DC beadTM + Sorafenib ✔ ✔ ✔

2. Nicolini et al. 2010: DC beadTM prior transplantation ✔ ✔

4. Aloia et al. 2007: Interval of efficacy for TACE prior transplant

DC BeadTM in Early and Late Stages:

Clinical series in HCC

Storage time of 14 days when loaded

CE Mark for loading Reproducible and

1. Jordan et al. 2010: DC BeadTM vs HepaSphere

Materials for Pharmacist

Stability data brochure

Establish market for

DEBIRI™ is a well-tolerated liver-directed therapy that

Target Leverage Build solid

Messaging to Medical Oncologist

DEBIRITM with DC BeadTM may give certain DEBIRITM with DC BeadTM

Note: Speak to reference centre/medical team before starting a programme!

3. Martin et al. 2009: Concomitant with systemic therapy (2nd–line) ✔

4. Fiorentini et al. 2012: Salvage therapy ✔ ✔

Materials for Medical Oncologist

DEBIRITM medical oncology brochure

Messaging to Surgical Oncologist

DEBIRITM with DC BeadTM as DEBIRITM with DC BeadTM DEBIRITM with DC BeadTM

Note: Speak to reference centre/medical team before starting a programme!

1. Martin et al. 2012: Concomitant with systemic therapy (1st –line) ✔ ✔

2. Bower et al. 2011: Downstaging unresectable patients ✔

3. Poston G. Presentation IHPBA Paris 2012: Neoadjuvant prior to resection

Materials for Surgical Oncologist

DEBIRITM surgical oncology brochure

Messaging to Interventional Radiologist

DEBIRITM with DC BeadTM may give certain

Note: Speak to reference centre/medical team before starting a programme!

1. Martin et al. 2012: Concomitant with systemic therapy (1st –line) ✔ ✔

2. Bower et al. 2011: Downstaging unresectable patients ✔

3. Poston G. Presentation IHPBA Paris 2012: Neoadjuvant prior to resection

Materials for Interventional Radiologist

Objections handling steps

Listen to the Objection