Role of molecular targeted therapy in HCC Dubai

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical Challenge

By

Heba El-Zawahry M.D.Prof. Medical OncologyHead of Medical Oncology DepartmentNational Cancer Institute, Cairo University

Role of Molecular Targeted Therapy in HCC

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeMalignant Transformation

Multistep (pathogenesis of HCC)

Potential TargetsOxidative stress and

inflammationViral oncogenes Carcinogens

Growth factors Telomere shortening

Cancer stem cells

Loss of cell cycle checkpoints

Antiapoptosis Angiogenesis

Normal liver

Liver cirrhosis

Hepatitis CHepatitis B

EthanolNASH

Epigenetic alterationsGenetic alterations

HCC[2]

Dysplastic nodules[1]

1. Tornillo L, et al. Lab Invest. 2002;82:547-553. 2. Verslype C, et al. AASLD 2007. Abstract 24.


Prognostic factors in HCC: dismal prognosis

Prognosis of HCC and treatment options are determined by

– A natomical extent of tumor (stage)

– B iological aggressiveness (grade)

– C irrhosis severity and functional status

– D isease extension; through staging workup include multiphase CT/MRI of abdomen, chest CT, and bone scan


Anatomic Staging : TNM

Goodman J, et al. Arch Surg. 2005;140:459-464.

Stage TNMI Single tumor < 2 cmII 1 tumor 2-5 cm or 2 or 3 tumors, largest < 3 cmIII 1 tumor > 5 cm or 2 or 3 tumors, largest > 3 cm

IV4 or more intrahepatic tumors or vascular invasion or

extrahepatic metastasis


Survival by HCC Tumor Stage

Survival of HCC is strongly related to stage at diagnosis

Earlier detection of HCC could improve outcome

Stravitz RT, et al. Am J Med. 2008;121:119-126.

II

III

IV

I

0

0.2

0.6

0.4

0.8

1.0

0 1 2 3 4 5Yrs

Surv

ival

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeChild-Pugh Classification of Severity of Liver

Cirrhosis and functions

Pugh RN, et al. Br J Surg. 1973;60:646-649. Lucey MR, et al. Liver Transpl Surg. 1997;3:628-637.

Measure 1 Point 2 Points 3 PointsBilirubin, mg/dL < 2.0 2.0-3.0 > 3.0

Albumin, g/dL > 3.5 2.8-3.5 < 2.8

Prothrombin time, sec < 4.0 4.0-6.0 > 6.0

Ascites None Slight Moderate

Encephalopathy, grade None I-II III-IV

Grade Total Points Surgical Risk 2-Yr Survival, %

A (well-compensated disease) 1-6 Good 85

B (significant functional compromise) 7-9 Moderate 60

C (decompensated disease) 10-15 Poor 35


Biologically Aggressive HCC

Features– Microvascular invasion– Satellite nodules– Diffuse infiltrating growth– Poorly differentiated– Mixed cholangio-

carcinoma– Bad molecular signature– FDG-PET scan positive– High AFP and AFP-L3%– Rapid growth

Associated with– Early metastasis– High risk of recurrence

after resection or liver transplantation

– Failure of local control with RFA/TACE

– Poor prognosis There is no consensus on

how to incorporate biology into tumor staging


Treatment Options for HCC

Curative (stage I-II)

– Thermal ablation (radiofrequency, microwave)

– Resection (partial hepatectomy)

– Liver transplantation (total hepatectomy)

Palliative (stage III-IV)

– Transarterial therapies

– Systemic therapy

– Targeted therapy

Out of each 10 HCC patients only one can be

offered curative intent therapy. (~10%)


New Therapies Under Investigation

Targeted therapy and Chemotherapy

Sorafenib (Nexavar) Erlotinib (Tarceva) Sirolimus (Rapamune) Capecitabine (Xeloda) Floxuridine (FUDR) Bevacizumab (Avastin) Sargramostim (Leukine) Oxaliplatin (Eloxatin) Imatinib (Gleevac)

Local Therapy Radiation Therapy

– 90Yttrium microspheres (Therasphere/SIRsphere)

– Stereotactic RadioSurgery (Cyberknife)

Doxorubicin Eluting Beads (DC Bead)

Photoactive chemicals (Litx)

HIFU


Systemic Therapy for HCC


Systemic chemotherapy/hormone therapyno proven efficacy in the treatment of advanced HCC

Trial Phase N Objective response, %

Systemic chemotherapyDoxorubicin as a single agent 2/3 203 10Doxorubicin combination (PIAF) 2/3 144 24Cisplatin 2 28 15Epirubicin 2 62 11Mitoxantrone 2 22 27Irinotecan, paclitaxel, gemcitabine, 5-fluorouracil 2/3 < 10

Anti-androgen (flutamide + leuprorelin) 3 376 No benefit vs. controlInterferon 3 30 < 10Octreotide 3 35 < 5Seocalcitol 3 746 < 5

PIAF = cisplatin, IFN α-2b,doxorubicin, adriamycin, and 5-fluorouracil.


1. Villanueva A, et al. Gastroenterology. 2008;135:1972-83.2. Tovar V, et al. J Hepatol. 2010; 52:550-9.

3. Newell P, et al. J Hepatol. 2009;51;725-33.

Growth factor signaling pathways in HCC:upregulated proliferation pathways

• IGF-IR, p-AKT, p-ERK, and p-S6 are differentially expressed in malignant vs. nonmalignant tissue (p < 0.01)

10x

p-Akt

10x

20x

p-ERK

20x 20x

p-S6

20x

Cirrhosis HCC

IGF-IR

20x 20x

Cirrhosis HCC

IGF-IR expressed in 16/79 (20%) of HCC samples

p-AKT expressed in 29/92 (31%) of HCC samples

p-ERK expressed in 8/78 (10%) of HCC samples*,3

p-S6 expressed in 41/86 (48%) of HCC samples

*47/78 (60%) tumors contained positive endothelial cells.


Molecular pathogenesis of HCC hepatocyte transformation can occur in the context of

inflammation, regeneration, hyperplasia, cirrhosis, and genetic or epigenetic alterations

Cellular signaling pathways that are often dysregulated in HCC include1,2

– VEGF/VEGFR2 → tumor neoangiogenesis

– RTK/Ras/Raf/MEK/ERK → tumor cell proliferation

– RTK/PI3K/Akt/mTOR → tumor cell survival

– Wnt/β-catenin → de-differentiation

1. Thorgeirsson S, et al. Hepatology. 2006;43(2 Suppl 1):S145-50.2. Avila MA, et al. Oncogene. 2006;25:3866-84.

Key pathways

and targets for

molecular therapy

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeTargeted Therapy:

Multispecific, blocks tyrosine kinase receptors regulating tumor proliferation and angiogenesis

Wilhelm SM, et al. Cancer Res. 2004;64:7099-7109. Wilhelm SM, et al. Mol Cancer Ther. 2008;7:3129-3140.

RAS

Vascular cell

Angiogenesis:

VEGFF

VEGFR-2PDGFR-

Paracrine stimulation

Mitochondria

Apoptosis

Tumor cell

PDGFVEGF

EGF / HGF

ProliferationSurvival

Mitochondria

HIF-2

Nucleus

Autocrine loop

Apoptosis

ERK

RAS

MEK

RAF

Nucleus

ERK

MEK

RAF

Differentiation

Proliferation

Migration

Tubule formation

PDGF-EGF/HGF

Sorafenib


Targeted therapy of HCC: Sorafenib

Prior to 2007, no therapy was of benefit in advanced HCC

SHARP trial: patients with advanced HCC randomized to sorafenib 400 BID vs placebo

Sorafenib delayed progression and prolonged survival from 7.9 to 10.7 mos

Led to approval by the FDA in 2008 for palliation of advanced-stage HCC

Llovet J, et al. N Engl J Med. 2008;359:378-390.

SorafenibPlacebo

P < .001

Time to Radiologic Progression

Mos Since Randomization0 1 2 3 4 5 6 7 8 9 10 11 12

1.00

0.75

0.50

0.25

0

Prob

abili

ty o

f Rad

iolo

gic

Prog

ress

ion

299 267 155 101 91 65 37 23 18 10 4 2 0303 275 142 78 62 41 21 11 10 3 1 1 0

Pts at Risk, nSorafenibPlacebo

SorafenibPlacebo

P < .001

OS

Mos Since Randomization

1.00

0.75

0.50

0.25

0Prob

abili

ty o

f Sur

viva

l

Pts at Risk. nSorafenibPlacebo

0 1 2 3 4 5 6 7 8 9 10 11 1213141516 17

299 290 270 249 234 213 200 172 140 111 89 68 48 37 24 7 1 0

303 295 272 243 217 189 174 143 108 83 69 47 31 23 14 6 3 0

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengePhase III SHARP Study: Sorafenib vs Placebo in

Advanced HCC

Primary endpoints: OS, time to symptomatic progression

Secondary endpoint: TTP (independent review), disease control rate, safety

Llovet JM, et al. N Engl J Med. 2008;359:378-390.

Patients with advanced HCC, Child-Pugh A,

ECOG PS ≤ 2, no previous systemic treatment

(N = 602)

Sorafenib 400 mg PO BID, continuous dosing

(n = 299)

Placebo 2 tablets PO BID, continuous dosing

(n = 303)


0 1 2 3 4 5 6 7 8 9 10 11 12

1.00

0.75

0.50

0.25

SorafenibMedian: 5.5 months(n = 299)

PlaceboMedian: 2.8 months(n = 303)

1.00

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

0.75

0.50

0.25

0 0

Time from randomization (months) Time from randomization (months)

Surv

ival

pro

babi

lity

Llovet JM, et al. N Engl J Med. 2008;359:378–90.

Time to progressionOverall survivalSorafenibMedian: 10.7 months (n = 299)

PlaceboMedian: 7.9 months(n = 303)

Prob

abili

ty o

f pro

gres

sion

OS and TTP in the SHARP trial: sorafenib prolonged OS by 44% and TTP by 73%

in patients with advanced HCC

HR = 0.58(95% CI: 0.45–0.74; P < 0.001)

HR = 0.69(95% CI: 0.55–0.87; P < 0.001)

TTP = time to progression.


Phase III Sorafenib vs Placebo in Asian Patients With Advanced HCC

No predefined primary endpoint

Secondary endpoints: OS, TTP, TTSP (FHSI-8), disease control rate (RECIST), safety

Patients with advanced HCC, Child-Pugh A, ECOG PS 0-2, no previous systemic treatment, life expectancy ≥ 12 wks

Stratified by macroscopic vascular invasion and/or extrahepatic

spread, ECOG PS, geographic region

Sorafenib400 mg PO BID

(n = 150)

PlaceboPO BID(n = 76)

Randomized 2:1

Cheng AL, et al. Lancet Oncol. 2009;10:25-34.

226 HCC patients


0

0.25

0.50

0.75

1.00

0 12 2214108642 1816 20

SorafenibMedian: 2.8 months(95% CI: 2.6–3.6)

PlaceboMedian: 1.4 months(95% CI: 1.3–1.5)

HR = 0.57(95% CI: 0.42–0.79; P < 0.001)

HR = 0.68(95% CI: 0.50–0.93; P = 0.014)

SorafenibMedian: 6.5 months(95% CI: 5.6–7.6)

PlaceboMedian: 4.2 months(95% CI: 3.7–5.5)

0

0.25

0.50

0.75

1.00

0 12 2214108642 1816 20

Cheng A-L, et al. Lancet Oncol. 2009;10:25–34.

Prog

ress

ion-

free

pro

babi

lity

OS and TTP in the Asia–Pacific trial: sorafenib prolonged OS by 47% and TTP by 74%

in patients with advanced HCC

Time to progressionOverall survival

Time from randomization (months) Time from randomization (months)

Surv

ival

pro

babi

lity

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeComparison between endpoints for the SHARP and

Asia–Pacific trials

Outcome Sorafenib

(n = 299)

Placebo(n = 303)

P

OS , months 10.7 7.9 <0.001

Time to symptomatic progression, months

4.1 4.9 0.77

response, %

CR 0 0 NA

PR 2 1 0.05

SD 71 67 0.17

Sorafenib(n = 150)

Placebo(n = 76)

P

6.5 4.2 0.014

2.8 1.4 0.0005

0 0

3.3 1.3

54.0 27.6

SHARP trial1 Asia–Pacific trial2

1. Llovet JM, et al. N Engl J Med. 2008;359:378–90.2. Cheng A-L, et al. Lancet Oncol. 2009;10:25–34.


Drug-related AEs,* %

Sorafenib(n = 86)

Placebo(n = 89)

Grade Grade Any 3/4 Any 3/4

HFSR 20.9 7.0/0 4.5 0/0

Diarrhea………………………….. 44.2 7.0/0 13.5 3.4/0

Alopecia 15.1 0/0 4.5 0/0

Fatigue…………………………... 24.4 3.5/1.2 21.3 3.4/0

Rash/desquamation 18.6 2.3/0 12.4 0/0

Weight loss 11.6 3.5/0 2.2 0/0

Anorexia 12.8 0/0 4.5 1.1/0

Nausea………………………….. 14.0 0/0 7.9 1.1/0

Abdominal pain (NOS) 10.5 4.7/0 2.2 0/0

Pruritis 9.3 0/0 11.2 0/0

*Reported in ≥ 10% of patients

AE profile in the SHARP study

Galle P, et al. J Hepatol. 2008;50 suppl 2:S372 [abstract 994]. Presented at EASL 2008.


SHARP Trial ; subanalysis

SorafenibPlacebo

0

4

6

8

10

12

14

16

MVI and EHS

HR = 0.7795%CI:

0.60–0.99

ECOGPS 1/2

HR = 0.7195%CI:

0.52–0.96

ECOGPS 0

HR = 0.6895%CI:

0.50–0.95

OverallSHARP

population

10.7

7.9

HR = 0.6995%CI:

0.55–0.87

Intermediate*HCC

HR = 0.7295%CI:

0.38–1.38

AdvancedHCC

HR = 0.7095%CI:

0.56–0.89

No MVIor EHS

HR = 0.5295%CI:

0.32–0.85

10.2

14.5

11.4

14.5

n =

161

n =

164

n =

138

n =

139

n =

90 n =

91 n =

209

n =

212

n =

54 n =

51 n =

245

n =

2522

PriorTACE

HR = 0.7595%CI:

0.49–1.14

n =

86 n =

90

Med

ian

OS

(mon

ths)

SHARP subanalysis shows a trend of survival benefit in patients with prior TACE treatment, in patients without MVI/EHS and in patients with

intermediate HCC

*Intermediate patients = BCLC B patients in SHARP trial.

11.9

9.9

Bruix J, et al. J Hepatol. 2012;57:821–9.

n =

299

n =

303


Primary endpoint: Recurrence-free survivalSecondary endpoints: Time to recurrence Overall survival

STORM adjuvant trial: Sorafenib vs placebo after curative resection/ablation

Stratification:

-Resection vs local ablation

-Intermediate vs high risk of recurrence

-Child–Pugh A vs B

-Geographical region

Sorafenib

400 mg p.o. b.i.d.

Continuous dosing

Ran

dom

izat

ion

N =

110

0Placebo

2 tablets p.o. b.i.d.

www.clinicaltrials.gov/ct2/show/NCT00692770.

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeBiomarkers for Sorafenib?

Not Ready for Prime Time !!

Tissue Biomarkers Nuclear pERK IHC 2-4+

associated with prolonged TTP in phase 2 study of sorafenib[1]

– 33/137 (24%) had available tissue for pERK testing; 18/33 scored 2-4+

Tissue pERK staining was not associated with outcomes in SHARP[2] (N = 110/602, 18%)

Circulating Biomarkers Plasma biomarkers studied in

SHARP trial[3] (N = 491/602, ~ 81%) – Baseline ↑ sc-Kit, ↓ HGF (SOR

arm) and ↓ Ang2 and ↓ VEGF (placebo arm) associated with ↑ OS in multivariate analyses

– sVEGFR2, sVEGFR3, Ras, EGF, FGF, IGF2 were not prognostic

None predicted benefit– Trend towards improved OS in

subset with baseline ↑ sc-Kit in SOR arm over placebo

1. Abou-Alfa GK, et al. J Clin Oncol. 2006;24:4293-4300. 2. Llovet JM, et al. N Engl J Med. 2008;359:378-390. 3. Llovet JM, et al. Clin Cancer Res. 2012;18:2290-2300.

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeLight Trial multicenter multinational randomized clinical trial for

the use of linifenib vs sorafenib in advanced HCC

900 HCC (A/B)

Randomized between sorafenib 400mg bid vs linifenib 400mg bid for 28days to be continued

Evaluation after 4 months

RECIST response

Radiological response

Interim report March 2013

Non inferiority result for Linifenib

Diarrhea and neutropenia were more in Sorafenib arm

DFP was superior in Sorafenib arm bur NS


Egyptian National trial for Sorafenib vs Sorafenib and UFT for systemic treatment of advanced HCC

Egyptian Trial include 5 big centers

Aimed for 715 advanced HCC

Randomized between Sorafenib vs Sorafenib and UFT as first line of treatment for HCC

Started November 2011 still ongoing

Recruitment of more than 100 cases up till now

Still interim analysis not yet

The advantage of this study is to evaluate the response of HCC following HCV in one genotype with some basic biological marker that may identify a target to HCC following this genotype


Beyond Sorafenib: New Agents in HCC

Agent Molecular Targets Phase Response,

%Median OS,

MosMedian TTP,

MosMedian PFS,

MosSafety:

Grade 3-4 AEs, %

Doxorubicin ± sorafenib[1] II PR: 4.0 13.7 6.4 6.0

Fatigue (6)Hand–foot skin

reaction(6.4)

Sunitinib[2]

VEGFR, PDGFR,

FLT3, KIT, RET

III CR+PR: <7 7.9 4.1 3.6Significant toxicities;

discontinued

Brivanib[3] VEGFR, FGFR II ORR: 4.3 9.8 1.8 2.0

HTN (7.3)Diarrhea (6.5)

Headache (4.3)

Linifanib (ABT-869)[4]

VEGFR, PDGFR II ORR: 6.8 9.7 3.7 NR HTN (18)

Fatigue (14)

Cabozantinib (XL184)[5]

c-MET, VEGFR2 II PR: 9.0 NR NR 4.2

Hand-foot syndrome (15)

Diarrhea(9)TP (9)

Tivantinib(ARQ197)[6] c-MET II NR MET high: 7.2 MET high: 2.9 MET high: 2.4 Neutropenic

sepsis (4.2)

1. Abou-Alfa GK, et al. JAMA. 2010;304:2154-2160. 2. Cheng A, et al. ASCO 2011. Abstract 4000. 3. Finn RS, et al. Clin Cancer Res. 2012;18:2090-2098. 4. Toh H, et al. ASCO 2010. Abstract 4038. 5. Cohn AL, et al. ASCO GI. 2012. Abstract 261. 6. Rimassa, L, et al. ASCO 2012. Abstract 4006.

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeMolecular classification of HCC

HCC genomic-based classification In a meta-analysis of 603 HCC patients

– 3 HCC subtypes were observed: S1–S3

– Distinguished by molecular phenotype, tumor size, cellular differentiation, and AFP levels

S1 S2 S3

Molecular pathways

TGF-βWnt MYC

AKT

Retained hepatocyte-like phenotypeE2F1 , p53

IFN

Published subclasses

Poor survival Good survival

Proliferation CTNNB1

Late TGF-β EpCAM (+)

Clinical phenotype

Moderately/poorly differentiated Well differentiated

Large tumor Smaller tumor

AFP Hoshida Y, et al. Cancer Res. 2009;69:7385–92.


Tivantinib (ARQ 197): Target MET in HCC

Ongoing efforts to study hepatocarcinogenesis have identified an important role for c-MET signaling in the promotion of tumor growth, angiogenesis, and metastasis. – Only known receptor for hepatocyte growth factor

– Correlated with poor prognosis

c-MET inhibitors fhave been evaluated in many phase I tilas for or more rational clinical trial design.

Tivantinib is a selective oral MET inhibitor

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeTivantinib vs Placebo in Previously Treated

Unresectable HCC

Multicenter, randomized phase II trial

Primary endpoint: TTP Stratification: MET status, HBV vs HCV, and duration of previous therapy Crossover on PD

Rimassa L, et al. ASCO 2012. Abstract 4006.

Patients with unresectable HCC following failure of

1 systemic therapy, ECOG PS < 2

(N = 107)Placebo PO BID

(n = 36)

Tivantinib 360 mg PO BID(n = 38)

Tivantinib 240 mg PO BID(n = 33)

clinicaloptions.com/oncologyMultidisciplinary Approaches to a Growing Clinical ChallengeTivantinib vs Placebo in Previously Treated

Unresectable HCC

MET level predictive of tivantinib benefit: TTP and OS similar with tivantinib vs placebo among patients with low MET expression

ITT

Rimassa L, et al. ASCO 2012. Abstract 4006.

MET Diagnostic High Population

Prop

ortio

n of

Pat

ient

s Pr

ogre

ssio

n Fr

ee

1.0

0.8

0.6

0.4

0

0.2

Wks to Tumor Progression0 10 20 30 40 50 60

Median TTP6.9 wks6.0 wks

TivantinibPlacebo

Patients7136

Events4630

HR: 0.64 (90% CI: 0.43-0.94;log-rank P = .04)

Prop

ortio

n of

Pat

ient

sSu

rviv

ing

1.0

0.8

0.6

0.4

0

0.2

Wks From Date of Randomization0 5 10 15 20 25


TivantinibPlacebo

Patients7138

Events5630

HR: 0.90 (90% CI: 0.57-1.40;log-rank P = .63)

Prop

ortio

n of

Pat

ient

s Pr

ogre

ssio

n Fr

ee

1.0

0.8

0.6

0.4

0

0.2

Wks to Tumor Progression0 10 20 30 40


TivantinibPlacebo

Patients2215

Events1413

HR: 0.43 (95% CI: 0.19-0.97;log-rank P = .03)

Prop

ortio

n of

Pat

ient

sSu

rviv

ing

1.0

0.8

0.6

0.4

0

0.2

Mos From Date of Randomization0 5 10 15 20


TivantinibPlacebo

Patients2215

Events1715

HR: 0.38 (90% CI: 0.18-0.81;log-rank P = .01)


• Imaging every 3–6 months for 2 years, then every 6–12 months

• AFP, if initially elevated, every 3–6 months for 2 years, then every 6–12 months

Options:• Sorafenib

(Child–Pugh class A [category 1] or B)c, d, e, f

• Chemotherapy + RT only in the context of a clinical trial• Clinical trial• Locoregional therapya

• RT (conformal or stereotactic)v (category 2B)• Supportive care• Systemic or intra-arterial chemotherapy in clinical trial

Options:• Sorafenib

(Child–Pugh class A [category 1] or B) c, d, e, f

• Clinical trial• Locoregional therapya

• RT (conformal or stereotactic)g (category 2B)

• Sorafenib(Child–Pugh class A [category 1] or B) c, d, e, f

• Supportive care• Clinical trial

SurveillanceTreatmentClinical presentation • Transplant

• Consider bridging therapy as indicated

Transplantcandidate

• Inadequate hepatic reservec

• Tumor location

Evaluate whether patient is a candidate for transplant (See UNOS criteria under Surgical Assessment HCC-5)b Not a

transplant candidate

Extensive liver disease

Unresectable

Inoperable by Perfomance Status or comorbidity, local disease only

Metastatic disease


Portal pressure/bilirubin

HCC

RFA Sorafenib

Stage 0PST 0, Child–Pugh A

Very early stage (0) 1 HCC < 2 cm

Carcinoma in situ

Early stage (A)1 HCC or 3 nodules

< 3 cm, PST 0

End stage (D)

Liver transplantation TACEResection Symptomatictreatment (20%)

Survival < 3 monthsCurative treatments (30%)

5-year survival 40–70%Palliative treatments (50%)

Median survival 11–20 months

Associated diseases

YesNo

3 nodules ≤ 3 cm

Increased

Normal

1 HCC

Stage DPST > 2, Child–Pugh C

Intermediate stage (B)Multinodular,

PST 0

Advanced stage (C) Portal invasion, N1, M1, PST 1–2

Stage A–CPST 0–2, Child–Pugh A–B

Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.

Barcelona Clinic Liver Cancer (BCLC) staging system and treatment strategy


Conclusions Early-stage HCC may be

cured with

– Thermal ablation

– Resection

– Liver transplantation

Advanced-stage HCC may be palliated with

– TACE or XRT

– Sorafenib/or as adjuvant

– Experimental therapies

Local measures often fail in tumors with aggressive biology

Application of therapies may be limited by severity of cirrhosis

Choosing the optimal treatment requires collaboration of multiple specialties


Thank You

Heba El-Zawahry M.D.

Health & Medicine

Role of molecular targeted therapy in HCC Dubai