Are we making any progress at all in the treatment of Advanced - - PowerPoint PPT Presentation

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Are we making any progress at all in the treatment of Advanced - - PowerPoint PPT Presentation

Oct 11, 2022 581 likes •794 views

Are we making any progress at all in the treatment of Advanced hepatocellular carcinoma? Bert H. ONeil, MD Cusick Professor of Oncology Director, GI and Phase I Clinical Trials IU Simon Cancer Center Disclosures Amgen Inc, Bayer

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Are we making any progress at all in the treatment of Advanced hepatocellular carcinoma?

Bert H. O’Neil, MD Cusick Professor of Oncology Director, GI and Phase I Clinical Trials IU Simon Cancer Center

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Disclosures

Advisory Committee Amgen Inc, Bayer HealthCare Pharmaceuticals, Genentech BioOncology

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Introduction

  • Most HCC is diagnosed at advanced stage (

e (ie e ie, Most HCC is d M unresectable diagn C is d le le/non agn

  • n
  • n-
  • sed at advance

no agn n-transplantable)

  • Therapeutic choices for advanced HCC depend on

Therapeutic choices for advance T tumor and liver characteristics

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RAS

Endothelial cell or Pericyte

Angiogenesis:

PDGF-β VEGF

VEGFR-2 PDGFR-β

Paracrine stimulation

Mitochondria

Apoptosis

Tumor cell

PDGF VEGF EGF/HGF Proliferation Survival

Mitochondria

EGF/HGF

HIF-2

Autocrine loop Apoptosis

ERK RAS MEK RAF

Nucleus

ERK MEK

  • RAF

Differentiation Proliferation Migration Tubule formation

  • Nucleus
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SLIDE 7
  • Sorafenib 400 mg p.o. bid

(n = 299)

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  • Hazard ratio (S/P): 0.69 (95% CI; 0.55 - 0.87)

P < 0.001

Survival Probability Sorafenib Median: 46.3 weeks (10.7 mo) (95% CI; 40.9 - 57.9) Placebo Median: 34.4 weeks (7.9 mo) (95% CI; 29.4 - 39.4)

1.00 0.75 0.50 0.25 8 16 24 32 40 48 56 64 72 80 W eeks

Patients at risk Sorafenib: Placebo: 299 303 274 276 241 224 205 179 161 126 108 78 67 47 35 25 12 7 2

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Years then passed….

Brivanib Sunitinib Everolimus Erlotinib

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Regorafenib

11

Target Oncol. 2015; 10(2): 199–213.

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Regorafenib in HCC

  • Bruix J et al, ESMO World GI Congress, 2016 Abstract LBA03
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REGO Adverse Events

  • Bruix J et al, ESMO World GI Congress, 2016 Abstract LBA03
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Overall Survival

RECIST 1.1 RR 6.6%

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What Else Is Out there?

  • Awaiting results of
  • f lenvatinib

b phase III trial (versus Awaiting re A sorafenib e ng re ib ib)

  • cMET

T inhibition for

  • r cMET

T + (amplified, cMET c T nhibition fo in

  • r M

cM

  • verexpressing?) HCC
  • Combination immunotherapy strategies
  • Strategies based on molecular characterization (FGFR,

Strategies based S CDK4/6, etc.)