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

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

Disclosures Amgen Inc, Bayer HealthCare Advisory Pharmaceuticals, Genentech BioOncology Committee

Introduction • Most HCC is diagnosed at advanced stage ( Most HCC is d M C is d diagn agn agn no osed at advance e (ie ie, e unresectable le/non le on- on n-transplantable) • Therapeutic choices for advanced HCC depend on Therapeutic choices for advance T tumor and liver characteristics

��

�� Tumor cell Endothelial cell or Pericyte Autocrine Paracrine EGF/HGF PDGF- β VEGF loop stimulation PDGFR- β VEGFR-2 Apoptosis RAS RAS RAF �� RAF �� Mitochondria MEK Mitochondria MEK Angiogenesis: HIF-2 EGF/HGF ERK Differentiation Apoptosis ERK Proliferation PDGF Migration VEGF Nucleus Tubule formation Nucleus Proliferation Survival ��

�� Sorafenib 400 mg p.o. bid �� (n = 299) ��

�� 1.00 Sorafenib Median: 46.3 weeks (10.7 mo) (95% CI; 40.9 - 57.9) 0.75 Survival Probability Placebo Median: 34.4 weeks (7.9 mo) (95% CI; 29.4 - 39.4) 0.50 0.25 Hazard ratio (S/P): 0.69 (95% CI; 0.55 - 0.87) P < 0.001 0 0 8 16 24 32 40 48 56 64 72 80 W eeks Patients at risk Sorafenib: 299 274 241 205 161 108 67 35 12 0 0 Placebo: 303 276 224 179 126 78 47 25 7 2 0 ��

Years then passed…. Brivanib Sunitinib Erlotinib Everolimus

��

Regorafenib 11 Target Oncol. 2015; 10(2): 199–213.

Regorafenib in HCC �� Bruix J et al, ESMO World GI Congress, 2016 Abstract LBA03

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

Overall Survival RECIST 1.1 RR 6.6%

��

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

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

individualizing treatment choices for people with IBD This is what we all want! We are not there

1. Making SpaceFor Reflection 2. NavigatingAndCommunicatingConstantChange 3. Making Progress

TRADITION PRIDE PROGRESS WATER TREATMENT PLANT WASTEWATER TREATMENT PLANT PARKS DEPARTMENT

National Vision for a Connected Future Getting There 1 Making Progress Vehicles Miles Driven |

Transformation of SGL Group making significant progress Dr. Jrgen Khler, CEO Dr. Michael

Annex B Department specific progress and data SME Progress Report Making government procurement

2016 Annual Meeting April 28, 2016 Making financial progress while making a difference Good

HIV, Health & Development 2019 The world is making progress on the The world is making

safely progress with an exercise program from treatment to survivorship Julie Everett DPT, CLT

An MCSAT treatment of Bit-Vectors (work-in-progress) Stphane Graham-Lengrand and Dejan

Recovery LIVE! Changing the Conversation: Shared Decision-Making in Treatment and Recovery

Making index insurance work: A review of recent progress Michael R. Carter University of

Control-Flow Hijacking: Are We Making Progress? Mathias Payer, Purdue University

Whole genome analysis to support cancer treatment decision making: The BC Cancer Agency

PUBLIC DECISION-MAKING ABOUT NEWBORN SCREENING IN CONTEXTS OF TREATMENT, INTERVENTION, AND

Evaluating Treatment Effects and Replicability - work in progress - Victor Gonzalez-Jimenez

Year 8 Parental Workshop Making the best progress Standards and Expectations Attendance:

From Waste Treatment to Resource Recovery How w ut utilities ar are mak making the transition

Greenwich CCG Governing Body 9 January 2019 1 Safety and quality We are making progress:

Annex B Department specific actions and data SME Progress Report Making government

Sir Michael Rake BT Group plc Chairman 2011 summary of the year Progress towards making BT a

Papua New Guineas progress towards climate compatible development THE DECISION MAKING PROCESS

Individual Progress Monitoring as a Data-Based Decision Making Tool Alex Freeman June 4, 2016

the Acoustic Soundscape making progress and quality Jukka Pajala Copenhagen, 30 September 2015

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

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

individualizing treatment choices for people with IBD This is what we all want! We are not there

1. Making SpaceFor Reflection 2. NavigatingAndCommunicatingConstantChange 3. Making Progress

TRADITION PRIDE PROGRESS WATER TREATMENT PLANT WASTEWATER TREATMENT PLANT PARKS DEPARTMENT

National Vision for a Connected Future Getting There 1 Making Progress Vehicles Miles Driven |

Transformation of SGL Group making significant progress Dr. Jrgen Khler, CEO Dr. Michael

Annex B Department specific progress and data SME Progress Report Making government procurement

2016 Annual Meeting April 28, 2016 Making financial progress while making a difference Good

HIV, Health &amp; Development 2019 The world is making progress on the The world is making

safely progress with an exercise program from treatment to survivorship Julie Everett DPT, CLT

An MCSAT treatment of Bit-Vectors (work-in-progress) Stphane Graham-Lengrand and Dejan

Recovery LIVE! Changing the Conversation: Shared Decision-Making in Treatment and Recovery

Making index insurance work: A review of recent progress Michael R. Carter University of

Control-Flow Hijacking: Are We Making Progress? Mathias Payer, Purdue University

Whole genome analysis to support cancer treatment decision making: The BC Cancer Agency

PUBLIC DECISION-MAKING ABOUT NEWBORN SCREENING IN CONTEXTS OF TREATMENT, INTERVENTION, AND

Evaluating Treatment Effects and Replicability - work in progress - Victor Gonzalez-Jimenez

Year 8 Parental Workshop Making the best progress Standards and Expectations Attendance:

From Waste Treatment to Resource Recovery How w ut utilities ar are mak making the transition

Greenwich CCG Governing Body 9 January 2019 1 Safety and quality We are making progress:

Annex B Department specific actions and data SME Progress Report Making government

Sir Michael Rake BT Group plc Chairman 2011 summary of the year Progress towards making BT a

Papua New Guineas progress towards climate compatible development THE DECISION MAKING PROCESS

Individual Progress Monitoring as a Data-Based Decision Making Tool Alex Freeman June 4, 2016

the Acoustic Soundscape making progress and quality Jukka Pajala Copenhagen, 30 September 2015

HIV, Health & Development 2019 The world is making progress on the The world is making