Carcinoma Hepatocelular

Manejo del paciente en el

estadio intermédio-avanzado

Flair José Carrilho

Professor
Division de Gastroenterologia y Hepatologia Clínica
Hospital das Clínicas
Facultad de Medicina de la Universidad de São Paulo
São Paulo, Brasil

fjcarril@usp.br
 South America Survey of HCC, 2016
Argentina, Brazil, Colombia, Ecuador, Perú, Uruguay
No. of patients = 1,336 - Predominance of HCV

Risk Factors

HCV - 48%
Alcohol - 22%
HBV - 14%
NAFLD - 9%
OTHERS - 8%

Chan AJ, Balderramo D, Kikuchi L, Ballerga EG, Prieto JE, Tapias M, Idrovo V, Davalos MB, Cairo F,
Barreyro FJ, Paredes S, Hernandez N, Avendaño K, Ferrer JD, Yang JD, Carrera E, Mattos AZ,
Hirsch BS, Gonçalves PT, Carrilho FJ, Roberts LR, Debes JD.
Early-age HCC associated with hepatitis B infection in South America.
Clin Gastroenterol Hepatol. 2017 May 19. doi: 10.1016/j.cgh.2017.05.015
 HCC in São Paulo
2010 – 2012 n = 364 patients
Etiology

26, 7%
201, 55%
32, 9%

57, 16% HCV

HBV
ALCOHOL
NAFLD
OTHERS

47, 13%

• Liver cirrhosis: 344 (95%)

• Non-cirrhosis: 20 ( 5%)
• Normal liver: 4
 South America Survey of HCC, 2016
No. of patients = 1,336 - Predominance of Late Diagnosis

HCC Screening Trends

%

75 53%
47%
50
25
0

Chan AJ, Balderramo D, Kikuchi L, Ballerga EG, Prieto JE, Tapias M, Idrovo V, Davalos MB, Cairo F,
Barreyro FJ, Paredes S, Hernandez N, Avendaño K, Ferrer JD, Yang JD, Carrera E, Mattos AZ,
Hirsch BS, Gonçalves PT, Carrilho FJ, Roberts LR, Debes JD.
Early-age HCC associated with hepatitis B infection in South America.
Clin Gastroenterol Hepatol. 2017 May 19. doi: 10.1016/j.cgh.2017.05.015
N = 884 N = 72

8%
13%

79%

BCLC A BCLC B BCLC C

HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Classification

34, 9% 9, 3%

121, 33%

115, 32%

85, 23%

0 A B C D
HCC new cases – last 6 months

103 new cases

number
BRUIX J, REIG M, SHERMAN M. HCC. LLOVET JM et al. HCC.
Gastroenterology 150:835-53, 2016. Nat Rev Dis Primers 2:1-23 , 2016.
BRUIX J, REIG M, SHERMAN M. HCC. LLOVET JM et al. HCC.
Gastroenterology 150:835-53, 2016. Nat Rev Dis Primers 2:1-23 , 2016.
HCC Intermediate - BCLC B

• Cirrhosis CHILD A ou B

• PST 0

• Multinodular

BRUIX J, REIG M, SHERMAN M.

Evidence-based Diagnosis, Staging, and Treatment of Patients with HCC.
Gastroenterology 150:835-53, 2016.
HCC
TACE: Efficacy and limitations
HCC
Current recommendations for TACE in treatment guidelines
HCC
Overall Survival in RTCs with TACE
HCC
Meta-analysis of RCTs comparing 2-year survival of
TAE/TACE versus best supportive care
 DEB-TACE vs c-TACE
Overall Survival

CHEN P et al. Evaluation of drug-eluting beads versus convenctional transcatheter

Arterial chemoembolization in patients with unresectable HCC: A systematic
Review and meta-analysis. Clin Res Hepatol Gastroenterol, 2016 (in press).
 DEB-TACE vs c-TACE
Survival Free of Recurrence

CHEN P et al. Evaluation of drug-eluting beads versus convenctional transcatheter

Arterial chemoembolization in patients with unresectable HCC: A systematic
Review and meta-analysis. Clin Res Hepatol Gastroenterol, 2016 (in press).
 DEB-TACE vs c-TACE
Conclusions:

• This Meta-analysis suggest a potential advantage of DEB-TACE with

better rates of:

• OVERALL SURVIVAL in 1-, 2- and 3-years, and

• SURVIVAL FREE OF RECURRENCE in 1- and 2-years when
compared with c-TACE.

CHEN P et al. Evaluation of drug-eluting beads versus conventional transcatheter

Arterial chemoembolization in patients with unresectable HCC: A systematic
Review and meta-analysis. Clin Res Hepatol Gastroenterol, 2016 (in press).
HCC Intermediate - BCLC B

• Perspectives

BRUIX J, REIG M, SHERMAN M.

Evidence-based Diagnosis, Staging, and Treatment of Patients with HCC.
Gastroenterology 150:835-53, 2016.
Radioembolization with Ytrio-90 – TARE
Overall Survival
HCC without Portal Vein Thrombosis HCC with Portal Vein Thrombosis

ROGNONI C et al. Trans-arterial radioembolization in intermediate-advanced HCC: Systematic

Review and Meta-analysis. www.impactjournals/oncotarget 2016.
 TARE
Tumor Progression Probability

HCC without PVT

HCC with PVT

ROGNONI C et al. Trans-arterial radioembolization in intermediate-advanced HCC: Systematic

Review and Meta-analysis. www.impactjournals/oncotarget 2016.
 TARE
Conclusions:

• The evidences suggest that TARE was indicated to treat

HCC based on Retrospective and Prospective Cohorts.

• Based on the evidences, until the randomized studies are

ongoing, TARE seems to be a viable option for patients with
HCC intermediate and advanced stages.

ROGNONI C et al. Trans-arterial radioembolization in intermediate-advanced HCC: Systematic

Review and Meta-analysis. www.impactjournals/oncotarget 2016.
 CHC Intermédio - BCLC B
Consideraciones Actuales
• CHC Multinodular confinado al hígado, con función hepática
preservada y sin sintomas relacionadas al cáncer.

• TACE és considerado el tratamiento “Gold standart”.

• Esfuerzos han mejorado los resultados com TACE, sendo la

técnica adecuada junto con la selección apropiada del paciente,
la clave para obtener buenos resultados.

FORNER A et al. Treatment of intermediate-stage HCC.

Nat Rev Clin Oncol 11:525-35, 2014.
 CHC Intermédio - BCLC B
Consideraciones Actuales
• Sorafenib, la única droga sistémica associada con benefício en
la sobrevida del CHC, puede ser considerada en el tratamiento
de los pacientes con BCLC estágio B no elegibles para TACE.

• TARE tiene eficácia antitumoral en pacientes con CHC en

estágio intermédio, pero tenemos que esperar por evidencias
sobre los benefícios de sobrevida.

FORNER A et al. Treatment of intermediate-stage HCC.

Nat Rev Clin Oncol 11:525-35, 2014.
 HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Classification – Therapy Proposed

HCC
Very Early Early Intermediate Advanced Terminal

BCLC 0 BCLC A BCLC B BCLC C BCLC D

18% 64% 18% 100% 100% 100%

Ressection Transplant PEI/RF TACE Sorafenib Paliative

HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Adherence to Treatment
Adherence to BCLC Treatment
No
Yes
 BCLC B
Intermediate Stage
HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Classification – Therapy Proposed = TACE
N=85

1% N=1

Indication Transplant

of TACE 6% N=5

Ressection
2% N=2
79%
Radioablation
N=67

12% N=10
TACE
Comorbidities
was done
HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Adherence to Treatment

BCLC B – Adherence to Treatment

No
Yes
 HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC B Adherence to Treatment
Survival

BCLC B – Impact:

Adherent
Benefit
Non-benefit

Time (months)
• Intermediate stage HCC is characterized by high heterogeneity,
which poses a great clinical challenge in terms of identifying the
most effective treatment for each individual patient.

• Curative interventions (HR, LT and RFA) may produce superior

outcomes in some intermediate stage patients with preserved liver
function.

• The management of BCLC B HCC patients often deviates from

this recommendation in the real world.
• Treatment stage migration allows the use of sorafenib in BCLC B
HCC patients who fail or have contraindications against TACE.

• International guidelines recommend TACE as the standard first-

line treatment for BCLC B HCC patients.

• The switch from TACE to sorafenib should be performed in due

time so as to avoid a deterioration of liver function caused by
TACE.
• The utility of treatment alternatives such as SIRT, radiotherapy and
immunotherapy remains to be evaluated in BCLC B HCC patients.

• Multimodal treatment approaches need to be further explored in

clinical trials in order to find the most effective treatment
combinations.
BRUIX J, REIG M, SHERMAN M. HCC. LLOVET JM et al. HCC.
Gastroenterology 150:835-53, 2016. Nat Rev Dis Primers 2:1-23 , 2016.
HCC Advanced - BCLC C
• Cirrhosis CHILD-PUGH A ou B

• PST 0-2

• Vascular invasion

• Extra-hepatic metastasis

BRUIX J, REIG M, SHERMAN M.

Evidence-based Diagnosis, Staging, and Treatment of Patients with HCC.
Gastroenterology 150:835-53, 2016.
LLOVET JM et al. HCC. Nature Reviews Dis Primers 2:1-23 , 2016.
 LLOVET JM et al. HCC.
Nat Rev Dis Primers 2:1-23 , 2016.
HCC
Sorafenib as 1st-line systemic therapy for uHCC
 Target Therapy: Sorafenib
Inhibit the Tyrosine kinase with interference on cellular proliferation and
angiogenesis
Tumor cell Vascular cell
VEGFF
Paracrine PDGF-b
Autocrine loop stimulation
EGF/HGF
PDGFR-b VEGFR-2
Apoptosis
RAS
RAS

RAF
RAF

Mitochondria Angiogenesis:
MEK
Mitochondria MEK
Differentiation
HIF-2
ERK EGF / HGF Proliferation
ERK
Apoptosis
PDGF Migration
Nucleus VEGF Tubule
Proliferation Nucleus
formation
Survival

Wilhelm SM, et al. Cancer Res. 2004;64:7099-7109. Wilhelm SM, et al. Mol Cancer Ther. 2008;7:3129-3140.
HCC
Overall Survival from two phase III trials
 Sorafenib

Real Life Studies

Sorafenib Experience
ICESP-USP1 (Brazil) X Asia-Pacific2 X SHARP3
Overall Survival ICESP: 16,3m
Asia-
ICESP-USP1 Pacific2 SHARP3
(N=46) (N=150) (N=299)
Overall survival, months
16.3 6.5 10.7
Duration of sorafenib, months
8.2 ND 5.3
Response rate by RECIST, %
Stable 50 54 72
Partial 1 3 2
Adverse events (grade 3 or 4)
Diarrhea 12 10 8
HFSR 6 6 8

1. Alencar RSSM, et al. 2016; 2. Cheng A, et al. 2009; 3. Llovet JM, et al. 2008
 Sorafenib Experience
ICESP-USP1 (Brazil) X Asia-Pacific2 X SHARP3
ICESP-USP1 Asia-Pacific2 SHARP3
(N=88) (N=150) (N=299)
Age (variation), yr 61 (23-78) 51 (23-86) 64 (21-89)
Sex (male), % 73 84 87

Etiology (HBV/HCV), % 9/68 70/10 19/29

Child-Pugh A, % 91 97 95

ECOG PS (0-1/2), % 59/41 95/5 92/8

BCLC (B/C), % 18/82 4/96 18/82

Extrahepatic spread, % 48 68 53
1. Alencar RSSM, et al. 2016; 2. Cheng A, et al. 2009; 3. Llovet JM, et al. 2008
 Manejo del paciente com Sorafenib
• Dosis inicial: 800mg/dia

• Ajustar la dosis de acuerdo con eventos adversos

→ “Follow-up rigoroso” (1º EA em ± 20 dias)

• Interrupcion transitória x interrupcion definitiva del

tratamiento → impactos diferentes en la sobrevida

• Presencia de EA dermatológicos → predictor de mejor

sobrevida.

Best Pratice and Res Clin Gastroent, 28, 2014

 Eventos Adversos
Dermatológicos:
• Síndrome manos-piés Diarrea
• Foliculitis Astenia
• Rash Anorexia
• Edema-Eritemas Hipertension Arterial
• Pápulas

Desarrollo de EA dermatológicos → predictor de mejor sobrevida.

• 147 hepatocellular carcinoma patients
• Follow up of 11.6 months (treatment duration 6.7 months), time to progression and
overall survival were 5.1 and 12.7 months.
• Development of dermatologic adverse events within 60 days of sorafenib initiation is
associated with better survival.
Better Management of Adverse Events Favors Sorafenib
Treatment of HCC Patients and Impact on Survival
Regiane Alencar 1,*, Luciana O. O. Kikuchi 1, Cláudia M. Tani 1, Aline L. Chagas
1, Cinira C. Camargo 1, Túlio E. F. Pfiffer 3, Paulo M.G. Hoff, Flair J. Carrilho 2

• 88 HCC patients treated with Sorafenib from June 2010 to January 2014
• Better survival was also observed in patients with AFP level < 100 ng/ml in the
last visit (p = 0.003).
• Overall survival was 16.7 and 36.7 months, in group A and B, respectively [OR
3.8; 95% CI 1.8-7.7; p<0.001].
J Cancer Therapy, 2016, 7, 275-284
J Cancer Therapy, 2016, 7, 275-284
The Impact of Early Dermatologic Events in the Survival of
Patients with Hepatocellular Carcinoma Treated with
Sorafenib
Fernanda Branco, Regiane S.M. Alencar, Fernanda Volt, Giovana Sartori, Andressa Dode,
Luciana Kikuchi, Claudia M. Tani, Aline L Chagas, Tulio Pfiffer, Paulo Hoff, Flair J Carrilho,
Angelo Alves de Mattos

• 127 pacientes tratados com Sorafenibe em 2 centros do Brasil de

2010 a 2014
• Cirrose:94%; CHILD A: 85,6%; BCLC C: 80,3%
• Invasão vascular e/ou metástases: 81%
• Eventos adversos: diarréia (62,2%) e reações dermatológicas (42%)
• Duração média do tratamento: 10m
• Sobrevida média: 19,9m
• Sobrevida maior nos pacientes com eventos dermatológicos (DAE:
31m x sem DAE: 14m, p <0,001)
Annals of Hepatology , 16 (2), Mar-Abril, 2017
HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC Adherence to Treatment

BCLC C – Adherence to Treatment

No
Yes
 HCC in São Paulo
2010 – 2012 n = 364 patients
BCLC C Adherence to Treatment

Survival
Survival

BCLC C – Impact:
Adherent
Benefit
Non-benefit

Time (months)
Time (months)
 Estudios con Quimioterapia Sistémica
Comparação Trial Linha Pacientes TTP (m) Sobrevida (m)
fase Tto (n)

DOXO + Sorafenib x II 1a 47 x 49 6,4 versus 2,8; 13,7 versus 6,5; RR = 0,49

DOXO RR=0,50 p=0,006

GEMOX + Sorafenib x II 1a 39 x 44 6,4 versus 2,8; 13,5 versus 13,0; RR=NA

Sorafenibe HR=NA p=0,68 p=0,11

Sorafenib + CAPOX II 1a 51 5,3 (IC 95% 3,8-5,9) 11,7 (IC 95% 8,9-15,4)

FOLFOX-4 x DOXO 1a 184 x 187 NR 6,4 vs 4,9

HOLLEBECQUE A et al. Eur J Cancer 51, 2015.

 Target Therapy - 1st Line
Estudo Drogas Desenho n Sobrevida RR p
(m)
ASIA- Sorafenib vs Superioridade 150 6,4 vs 4,2 0,68 0,01
PACIF placebo 76

SHARP Sorafenib vs Superioridade 229 10,7 vs 7,9 0,69 0,001

placebo 303
SUNITINIB Sunitinib vs Superioridade 530 7,9 vs 10,2 1,3 0,001
Sorafenibe 544
BRISK-FL Brivanib vs Não- 577 9,5 vs 9,9 1,06 0,31
Sorafenibe inferioridade 578
LIGHT Lifanib vs Não- 514 9,1 vs 9,8 1,04 0,52
Sorafenibe inferioridade 521

SEARCH Sorafenib / Erlotinib Superioridade 362 9,5 vs 8,5 0,92 0,48

vs Sorafenib / 358
placebo
THILLAI K et al. World J Gastro Oncol 8 (2), 2016.
HCC Advanced - BCLC C

• Perspectives

BRUIX J, REIG M, SHERMAN M.

Evidence-based Diagnosis, Staging, and Treatment of Patients with HCC.
Gastroenterology 150:835-53, 2016.
New Target Therapies for HCC

THILLAI K et al. World J Gastro Oncol 8 (2), 2016.

 Phase III Studies
Comparação Alvos terapêuticos Desenho Número NCT

1a Linha
VEGF, PDGFR, Levatinib versus
Levantinib FGFR,RET,SCFR sorafenibe NCT 01761266
2a linha
Regorafenibe VEGFR, Regorafenibe versus NCT01774344
PDGFR,BRAF, FGFR, placebo
KIT, RET
Tivatinibe versus NCT01755767
Tivatinibe c-MET placebo (em
pacientes com
hiperexpressão de
c-MET)
Carbozantinibe NCT01908426
Cabozantinibe c-MET, VEGFR,RET versus placebo

Chuma M et al, Hepatol Research, 45, 2015

 Table 1 | New drugs under evaluation in clinical trials phase 2 in HCC
Drug Phases Enrollment Trials Year
11C-Acetate Phase 2 18 1 2015
Principal targets ABC294640 Phase 2 39 1 2016
Anlotinib Phase 2 60 1 2016
in Phase 2 Apatinib
BBI503
Phase 1 & 2
Phase 2
100
60
3
1
2016
2014

clinical trials in ceritinib

CF102
Phase 2
Phase 2
30
78
1
1
2015
2014
Colchicine Phase 2 60 1 2013
HCC CPI-613
cytokine induced killer cells
Phase 2
Phase 1 & 2
100
13
1
1
2013
2013
Donafenib Phase 2 & 3 600 1 2015
ENMD-2076 Phase 2 29 1 2014
enzalutamide Phase 1& 2 217 1 2015
FGF401 Phase 1 & 2 168 1 2014
HCQ Phase 1 & 2 49 1 2013
Huachansu Phase 2 120 1 2012
Icaritin Phase 2 50 1 2013
ImFOLFOX6 Phase 2 300 1 2015
IMMU-132 Phase 1 & 2 250 1 2012
INC280 Phase 2 56 1 2012
LEE011 Phase 2 40 1 2015
LY2157299 Phase 2 190 1 2010
MLN0128 Phase 1 & 2 118 1 2015
MSC2156119J Phase 1 & 2 232 2 2013
OXY111A Phase 1 & 2 69 1 2014
Palbociclib Phase 1 & 2 50 1 2014
Pembrolizumab Phase 2 28 1 2016
TAI-GPC3-CART cells Phase 1 & 2 30 1 2016
Tefinostat Phase 1 & 2 69 1 2014
90Y-RE Phase 2 140 1 2011
Fendrix Phase 2 & 3 30 1 2015
Immuncell-LC Phase 2 78 1 2016
Melphalan Phase 2 73 2 2015
Pembrolizumab Phase 2 100 1 2016
TLC388 Phase 2 62 1 2014
Yttrium-90 Microspheres Phase 2 40 1 2013
Principal combinatory Therapies in Phase 2 clinical
trials in HCC
Table 2 | New combinatory therapies under evaluation in clinical trials phase 2 in HCC
Combinatory therapy Phases Enrollment Year
BBI608 or BBI503 and Sorafenib Phase 1 and 2 114 2014
CC-122 and Nivolumab Phase 1 and 2 50 2016
Durvalumab and Tremelimumab Phase 1 and 2 90 2016
Galunisertib and Nivolumab Phase 1 and 2 100 2015
Interferon Alfa and •
Fluorouracil Phase 2 66 2013
Leucovorin and Fluorouracil and Oxaliplatin and Sorafenib Phase 2 40 2013
LY2875358 and Ramucirumab Phase 1 and 2 100 2014
Pirarubicin and Oxaliplatin and Lipiodol Phase 2 and 3 164 2015
S-1 and Leucovorin Phase 2 32 2012
Sorafenib and Metformin Phase 2 82 2015
Sorafenib and S-1 and Oxaliplatin Phase 2 100 2014
Thalidomine and Tegafur-Uracil Phase 2 40 2014
TRC 105 and Sorafenib Phase 1 and 2 83 2011
Anti-NY ESO-1 mTCR PBL and Cyclophosphamide and Fludarabine and Aldesleukin Phase 2 43 2013
D-CIK and anti-PD-1 antibody Phase 1 and 2 50 2016
G-CSF and Growth Hormone Phase 2 and 3 150 2015
MEDI4736 and tremelimumab Phase 2 144 2015
Mitomycin and Epirubicin Phase 1 and 2 60 2015
Nivolumab or Sorafenib and Ipilimumab Phase 1 and 2 620 2012
PDR001 and INC280 Phase 1 and 2 108 2016
 Regorafenib

RESORCE - Fase II
• TTP 4,8 meses e sobrevida global de 13,8 meses
Efficacy and safety of regorafenib versus placebo in patients with HCC
Progressing on sorafenib: results of the international,
randomized phase 3 RESORCE trial

▪ Regorafenib, an oral multikinase inhibitor, in patients with

intermediate or advanced HCC who had disease progression on
Sorafenib.
▪ Double-blind placebo-controlled trial, BCLC B or C, who received
Sorafenib > 20 day at >400 mg/day with progression, Child-Pugh A,
ECOG status 0-1, randomized 2:1.
▪ Regorafenib 160 mg/day during weeks 1-3 of each 4-week cycle.
▪ Primary endpoint: OS – intent-to-treat.
▪ Secundary endopoints: PFS, TTP, RR, DCR.
BRUIX J et al. Ann Oncol 37(suppl 2):ii1-3 , 2016. doi:10.1093/annonc/mdw237.3
 Regorafenib
Overall survival (OS)
Primary endpoint
Regorafenib Placebo
n=379 n=194
Events 233 (61%) 140 (72%)
Censored 147 (39%) 54 (28%)
Median OS 10.6 months 7.8 months
(95% CI) (9.1, 12.1) (6.3, 8.8)
HR 0.63 (95% CI: 0.50, 0.79)
P<0.0001 (1-sided)

Bruix J et al. Lancet 389:56-66, 2017

 Regorafenib
Progression-free survival (PFS)
Regorafenib Placebo
n=379 n=194
Events 293 (77%) 181 (93%)
Censored 86 (23%) 13 (7%)
Median PFS 3.1 months 1.5 months
(95% CI) (2.8, 4.2) (1.4, 1.6)
HR 0.46 (95% CI: 0.37, 0.56)
P<0.0001 (1-sided)

Bruix J et al. Lancet 389:56-66, 2017

Based on mRECIST
 Regorafenib
Time to progression (TTP)

Regorafenib Placebo
n=379 n=194
Events 274 (72%) 173 (89%)
Censored 105 (28%) 21 (11%)
Median TTP 3.2 months 1.5 months
(95% CI) (2.9, 4.2) (1.4, 1.6)
HR 0.44 (95% CI: 0.36, 0.55)
P<0.0001 (1-sided)

Based on mRECIST Bruix J et al. Lancet 389:56-66, 2017

 Regorafenib
Subgroup analysis of Overall Survival

Bruix J et al. Lancet 389:56-66, 2017

 Regorafenib
Conclusions

• RESORCE met the primary endpoint demonstrating that regorafenib led to

a statistically significant and clinically meaningful improvement in OS for
patients with HCC who progressed on prior sorafenib treatment
– 37% reduction in the risk of death (HR 0.63; 95% CI 0.50–0.79 P<0.0001)
– Median OS 10.6 months vs 7.8 months
– Survival benefit was maintained in all predefined subgroups
• PFS and TTP were significantly improved with regorafenib and the benefit
was maintained in all predefined subgroups
• Patients treated with regorafenib had a significantly higher response rate
and a significantly higher and almost doubled disease control rate
• Adverse events were manageable and consistent with the known
regorafenib safety profile

Bruix J et al. Lancet 389:56-66, 2017

Immune Therapies
 Conclusiones
• CHC és un tumor heterogéneo con una compleja patogénesis y várias
vias de sinalización envolvidas en la hepatocarcinogénesis.

• Sorafenib és el único tratamiento sistémico aprovado para el CHC

avanzado.

• Estudios de fase III negativos

– Primera-linea: sunitinib,[1] erlotinib + sorafenib,[2] linifanib,[3]
brivanib[4]
– Segunda-linea: brivanib,[5] everolimus[6]

• Desafio: diversidade molecular del CHC

1. Cheng AL, et al. J Clin Oncol. 2013;31:4067-4075. 2. Zhu AX. ESMO 2012. Abstract LBA2. 3. Cainap C, et al. ASCO
GI 2013. Abstract 249. 4. Johnson PJ, et al. J Clin Oncol. 2013;31:3517-3524. 5. Llovet JM, et al. J Clin Oncol.
2013;31:3509-3516. 6. Zhu AX, et al. ASCO GI 2014. Abstract 172. 7. Finn RS. Clin Cancer Res. 2010;16:390-397.

• Hepatologia
• Prof. Dr. Flair J. Carrilho
• Dra. Aline L. Chagas
• Dra. Regiane S. M. Alencar
• Dra. Cláudia Tani
• Dra. Priscilla Brizolla
• Profa. Claudia Oliveira
• Ultra-sonografia
• Dra. Denise C. Paranaguá Vezozzo
• Patologia
• Prof. Dr. Venâncio A. F. Alves
• Prof. Dr. Evandro Sobroza de Mello
• Biologia Molecular
• Profa. Dra. Suzane Kioko Ono
• Prof. Dr. João Renato Rebello Pinho
Hospital das Clínicas da FMUSP
Instituto do Câncer do Estado de São Paulo
• Cirurgia do Fígado e Transplante Hepático
• Prof. Dr. Luiz Augusto Carneiro D’Albuquerque
• Prof. Dr. Paulo Herman
• Radiologia
• Prof. Dr. Manoel Rocha
• Dr Roberto Blasbalg
• Radiologia Intervencionista
• Prof. Dr. Francisco Carnevale
• Dr. Marcos Menezes
• Oncologia
• Prof. Dr. Jorge Sabbaga
• Prof. Dr. Paulo Hoff
• Dr Tulio Piffer
Gracias por la atención!