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Transarterial Chemoembolization

Kelly W. BurakMD, FRCPC, MSc (Epid)Associate Professor of MedicineUniversity of CalgaryDepartments of Medicine & Oncology

Director, Calgary Liver Unitand Southern Alberta Liver Transplant Clinic

Chair, IR Guidelines CommitteeAHS Provincial GI Tumour Group

@kwburak

Research support from:Bayer Bristol-Myers-SquibbGenentechSalixGlaxo-Smith-Kline

Consulting / Advisory Boards / Honorarium from:AstellasGileadJanssenNovartis

Kelly W. BurakDisclosures (past 24 months)

Overview

1) Evidence for TACE

2) DEBs vs cTACE

3) Bridging to LT

4) Combination with Sorafenib

5) When to abandon TACE?

median survival from ~ 16 20 months

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Systematic Review

• Technique

– No consensus chemo or particles

– Role of Lipiodol controversial

• Survival

– 1 yr = 62 20% / 3 yr = 30 15%

• Complications

– Post-embolization syndrome 60 – 80%

– Liver failure 0 – 49%

– Procedure related death 2.4% (0 – 9%)

Marelli L, et al. Cardiovasc Intervent Radiol 2007;30:6-25.

DEBs

DC-Bead [DEBDOX]100-300µM

HepaSphere

30-60µM

Doxorubicin Exposure

Varela M, et al. J Hepatol 2007;46:474-81.

DC-Bead

DEB versus cTACE

• Post-embolization syndrome similar

• Fewer liver toxicity

SAEs (9 vs 3)

• Less cardiotoxicity

LVEF DEB cTACE

No decrease 37% 29%

Non-substantial 18% 24%

Substantial 0% 6%

Not known 45% 42%

Vogel TJ, et al. Am J Roentgenol 2011;197:562-570.

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Better Survival with DEBs

• 104 pts (103 cirrhotic) treated with DEB

– 95% CP A, 63% HCV +

– 41 BCLC A / 63 BCLC B

• 24.5 mo median FU

– 2 LT / 24 sorafenib

• Median survival

– BCLC A = 54.2 mo

– BCLC B = 47.7 mo

– Censoring at LT / sorafenib = 47.7 mo

Burrel M, et al. J Hepatol 2012;56:1330-35.

Calgary TACE (2002-2010)

Characteristics cTACE (n=140) DEB (n=62) p value

Patients 65 34

# TACE/pt, median [range] 2 [1-6] 1 [1-5] NS

Male 73.9% 73.5% NS

Age, mean SE 66.7 1.4 59.4 1.9 0.003

HCV / HBV 38.5% / 21.5% 41.1% / 38.2% NS

LT performed 9.2% 8.8% NS

BCLC A / B 38.5% / 61.5% 41.2% / 58.6% NS

CP class A / B 58.7% / 41.3% 50% / 44.1% NS

Size largest lesion, mean 5.0cm 4.2cm NS

TTV, mean 393.9cm3 109.2cm3 NS

AFP, median 36.8ng/mL 28.5ng/mL NS

Overall Survival

Median OS [95%CI]

Overall cohort: 21.7 mo [15.8-30.9]

CP class A: 30.0 mo [20.1-42.0]

CP class B: 15.3 mo [12.0-18.7]

DEB: 26.5 mocTACE: 21.7 mo

Days after initial TACE

Pro

po

rtio

n S

urv

ivin

g

p=0.55

Survival Analysis

• Female sex associated with survival after TACE

– HR 3.7 [1.8-7.4], p<0.001– Adjusting for AFP, TTV, CP, age, LT listing, type & # of TACE

mortality HR [95% CI] mortality HR [95% CI]

TTV >115cm3 1.75 [1.00-3.07] Multiple TACE 0.51 [0.29-0.88]

AFP >400ng/mL 1.95 [1.08-3.52] Listing for LT 0.32 [0.12-0.89]

Ascites 2.37 [1.11-5.08] CP class A 0.51 [0.29-0.88]

ECOG PS 1 2.39 [1.36-4.21] Albumin 0.93 [0.87-0.99]

Male sex 0.33 [0.19-0.60]

Univariate analysis

Multivariate analysis

Complications & LOS

Characteristics cTACE (n=140) DEB (n=62) p value

Any Complication 86.2% 67.6% 0.029

Post-Embolization Syndrome 73.9% 23.5% <0.0001

Major Complications* 32.3% 11.8% 0.026

Death within 30 days 3 0# <0.001

Length of Stay, median [IQR] 3 days [2-5] 2 days [2-4] 0.011

*Major complications = Death within 30d, GI bleed, new ascites, SBP, encephalopathy, severe PES, vascular complications.

# Does not include 1 death in SPACE study and 1 death in 2012.

DEBs are Cost-Effective

Burak KW, et al. Can J Gastroenterol 2013; 27(Suppl A): 72A-73A.

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DEB vs cTACEOverall Survival

Song MJ, et al. J Hepatol 2012; 57: 1244-50.

Doxorubicin Exposure

HepaSphere

30-60µM

Malagari K, et al. Cardiovasc Intervent Radiol 2014; 37: 165-75.

Bridging to LT

Maggs JR, et al. Aliment Pharmacol Ther 2012; 35: 1113-1134.

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Combination Studies SPACE Study

Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.

TTP

Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.

Overall Survival

Lencioni R, et al. J Clin Oncol 2012; Suppl 4: LBA154.

Japan – Korea Study

• 458 CP A pts with unresectable HCC

• 25% tumour 1-3mo after 1st or 2nd TACE

• 1:1 sorafenib or placebo

• >50% started >9 wks after TACE

• Sorafenib dosing

• median = 386mg

• 73% dose reductions

• 91% dose interruptions

Kudo M, et al. Eur J Cancer 2011;37:212-20.

Japan – Korea Study

TTP

OS

Kudo M, et al. Eur J Cancer 2011;37:212-20.

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Japan – Korea Study

Kudo M, et al. Eur J Cancer 2011;37:212-20.

Median sorafenib

16 vs 31 wks

When to Abandon TACE?

Expert Recommendations

Adapted from Raoul JL, et al. Cancer Treat Rev 2011;37:212-20.

OPTIMIS

Study

SHARP Subgroup Analysis

p=NS

Bruix J, et al. J Hepatol 2012;57:821-829.

p=NS

BCLC Stage B Prior TACE

Sorafenibor

RCTs evaluatingSorafenib± TARESorafenib± SBRT

Conclusions

• TACE provides survival advantage for carefully selected patients (Level 1a)

• DEBs are a more standardized technique and are better tolerated (Level 1b)

– DEBs may offer a survival advantage (Level 2b)

• Bridging to LT may recurrence (Level 3b)

• Combination with sorafenib is not recommended (Level 1b)

• When to abandon TACE remains an area of controversy and requires further study

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Transarterial Chemoembolization

Kelly W. BurakMD, FRCPC, MSc (Epid)Associate Professor of MedicineUniversity of CalgaryDepartments of Medicine & Oncology

Director, Calgary Liver Unitand Southern Alberta Liver Transplant Clinic

Chair, IR Guidelines CommitteeAHS Provincial GI Tumour Group

@kwburak