Toni K. Choueiri, MD

Director and Disease Center Leader

The Lank Center for Genitourinary Oncology

President of Medical Staff

Dana-Farber Cancer Institute

The Jerome and Nancy Kohlberg Endowed Chair

Harvard Medical School

Boston, Massachusetts

@DrChoueiri

Eugene P. Schonfeld Lecture

“my RCC and non-RCC life path”

PART 1 (Y0-26)

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3

1975: Start of the Lebanese Civil War and the year I was born

(Lebanese Civil War: 1975-1990)

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1975 2016

Mary and Kozhaya Choueiri

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The Eternal Magic of BeirutFor many of us, it’s synonymous with war and strife. But for the

artists, chefs, designers, architects and scholars who live

there, Beirut will always be a place where ideas and beauty

flourished ... and flourish still.

By MICHAEL SPECTER, MAY 2, 2016

Beirut: The Middle East's party capitalBy Tim Hume, CNN

Updated 7:40 AM ET, Fri August 10, 2012

PART 2 (Y26-32)

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7

Cleveland: my American Birthplace (2001)

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Cleveland, the early years……

Not clear first going into GU or Kidney cancer

• Papers in:

– Benign Hematology (Lichtin, 1 )

– Breast Cancer (Budd, 4)

– Multiple Myeloma (Hussein, 5)

– Thrombosis in Cancer patients

(Deitcher, 2)

– Hodgkin lymphoma (Bolwell, 1)

– Skin (Olencki 1)

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Early Years (2003)

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• Also @Cleveland Clinic: 2003-2007:

•Derek Raghavan (Cancer Center Director)

•Rob Dreicer

•Eric Klein, Andy Novick (Urology)

•Tim Gilligan

•Jorge Garcia

•Brian Rini

•Ming Zhou (Pathology)

•Laura Wood, RN

•Brian Bolwell, Mikkael Sekeres (Heme)

•Paul Elson (Stats)

•Many co-fellows

COMPARZ Trial (2013)

Bernard Escudier and the French Connection (2003-

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2015 ESMO Presidential session 2016 ESMO Presidential session

Danny Heng: yes he believes In prognostication (psychic)

and no, he is not Irish (IMDC database Consortium)

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Calgary: Why he's a 2015 Top 40 under 40

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International mRCC Database ConsortiumCurrently includes 7500 patients from 35 institutions

International mRCC Database Consortium

Tissue Clinical Data

IMDC Biobank Repository

for Translational Research

(IMDC-BTR)

25+ Institutions, 10 countries

Biomarker Discovery + Validation

Tissue Microarrays

Primary and metastatic analyses

PART 3 (Y32-

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-47k employees

-22k students

-6500 job openings/year

-If LMA was a State=7th in NIH

funding

(LMA)

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The Longwood Area

Across the River: MGH, MIT,

Broad Institute, Harvard University,

Biotech (Novartis, Merck, Pfizer,

AZ, Abbott…)

Many colleagues, friends, mentors, fellows, bosses,

nurses, assistants…You learn from everyone…

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But a lot I learned from my patients and their families…

David McDermottBIDMC

Toni ChoueiriDFCI Othon IliopoulosMGHBill KaelinDFCI Dror MichaelsonMGH

Sabina SignorettiBWH

Kidney Cancer Program at Dana-Farber/Harvard Cancer Center

Study Drug Target Phase Status

Dalantercept ALK1 II Recruiting

X4P-001 CXCR-4 I Recruiting

Cabozantinib VEGF III Completed / Positive

Cabozantinib MET/Axl II Completed / Positive

PT-2385 HIF-2 I Recruiting

Discovery ImpactTranslation

And Mike Atkins who

started most this…

Kidney SPORE Co-leader

DF/HCC Kidney Cancer Program

Leader

-SELECT Trial

-Cytokine Working group

-Early trials with Nivolumab and

Atezolizumab.

And many more….

David McDermott, MD

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Fenway Park—Red Sox Nation!

Lasker Award Celebration for Bill Kaelin...(one of many)

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Harvard Urology SPORE Retreat @MGH, 2016

DFCI/MGH/BIDMC

Yale Cancer Center

MSKCC

MD Anderson

ASCO CDA

Bill Kaelin, MET and Cabozantinib, the real story...

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Sometime in 2009….

786-O VHL -/- cells with shRNA against MET

Median OS

mo (95% CI)

Cabozantinib (N=330) 21.4 (18.7-NE)

Everolimus (N=328) 16.5 (14.7-18.8)

Overall SurvivalAnd the rest is history….

Cabozantinib Activity in Sunitinib-Resistant Xenografts

Cabozantinib rescues acquired resistance to sunitinib in a RCC model Efficacy with cabozantinib was associated with inhibition of MET and AXL in vivo

Saline Sunitinib only

Sunitinib

+Cabozantinib

P-AXL

AXL

P-Met

Met

Zhou and Jonasch, et al. (2015) Oncogene .

Eric Jonasch, MDACC

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2015 IKCS, Miami

2016 ESMO, Copenhagen

2016 ASCO, Chicago

The impact of Angiotensin System Inhibitors (ASIs) in mRCC

McKay, et al, Clin Cancer Res. 2015

VEGF Inh.IFN-α

A-498 RCC cell line 769-P RCC cell line

The Renin-Angiotensin System Rana McKay Ronit Simantov, Pfizer

-Using Harvard database+ IMDC Cohort + Pfizer cohort + TCGA:

Body Mass Index FASN expression

15 International Centers, 1 Pharma and 6 disciplines:

• Urology

• Medical Oncology

• Statistics

• Computational Biology (TCGA)

• Epidemiology

• Pathology

Laurence Albiges

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Lauren Harshman

Phase III intergroup adjuvant PROSPER

PI: Harshman

Discipline Main Projects and work…

Fabio Schutz Med Onc MET SNP predicts recurrence in RCC, meta-

analyses of rare toxicities from TKIs

Andre Fay Med Onc mTOR pathways mutations and rapalogs, TKI

biomarkers

Guillermo DeVelasco Med Onc Biomarkers of RCC (TKI, immuneTX)

Monty Pal Med Onc Genomics of rare RCC tumors, cfDNA,

biomarkers in RCC. Also he went to college at

age 13

Quoc Trinh/Maxine Sun Urology and

Health

Service

Research

Health disparities in prostate cancer research,

Modern day application of cytoreductive

nephrectomy

Katherine Krajewski Radiology Novel radiologic biomarkers of response to TKIs

And many others: Urun,

Moreira, Lalani, Hamieh,

Mulane, Bossé….

…….. ….

Computational

Team/Broad Institute

Diana Miao

Stephanie Mullane

Eli Van Allen

The Patients

Lank Center for

GU Oncology

Joaquim Bellmunt

Rana McKay

Lauren Harshman

Mark Pomerantz

Craig Norton

Stats Team

SPORE P50 CA101942

DFCI/BWH/BIDMC/Harvard

Sabina Signoretti

Bill Kaelin

Dave McDermott

K. Mahoney

M. Giannakis

David Kwiatkowski

Gordon Freeman

Matt Freedman

US and International

collaborators

IMDC members

TCGA collaborators

Industry collaborators

Motzer

Tannir

Escudier/Albiges

Rini

Vaishampayan

Donskov

Porta

Brugarolas

Many more

Health Service Research

-Maxine Sun

-Paul Nguyen

-Steve Chang

-Quoc Trinh

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Dr. Mahoney (YIA) with Bill Bro Carrie Konosky, CEO

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Sue, Zeina and Samuel (Sam)