New Advances in Cancer

Treatment

ELIE FAHED, MD

efahed@rockymountainoncology.com

Presentation Overview

� Why Immunotherapy?

� Historical use : Case for IL-2

� Use of CTLA-4 inhibition: Focus on Yervoy

� Use of checkpoint inhibitors : Focus on anti-PD1

� Use of smart vaccines: Focus on Provenge

Immunotherapy

� Cancer immunotherapy attempts to stimulate the

immune system to reject and destroy tumors

� Hallmark of cancer pathogenesis: Avoid immune

destruction

� Patients on immunosuppressant have a two-fold increase

risk of common cancers and up to 20 fold increase of

non-melanoma skin cancer and NHL

Immunotherapy Made Simple

Cytokine Therapy

� Interleukin-2 for RCC and Melanoma

since 1998

� 5-10% long-term responders

�High toxicity and mortality, frequent ICU

admissions

�Use limited to medically fit patients who

can tolerate the side effects

Immunotherapy Made Simple

CTLA-4 inhibition

Yervoy in Melanoma

FDA approval March 2011

PET scan before and afterApril 2011 August 2011

Some patients Alive at 10 years and counting!

Yervoy Side Effects

� Clinically-significant inflammatory and immune toxicities

in approximately 15-20% of patients

� Most serious side effects include severe enterocolitis,

hepatitis, dermatitis, thyroiditis,……..any “itis”

� Black Box Warning for severe and fatal immune-mediated

adverse reactions due to T-cell activation and proliferation.

� High-dose corticosteroids therapy for severe immune-

mediated reactions

Immunotherapy Made Simple

Programmed Cell Death-1

� PD-1 is a protein on the surface of activated T cells

� If another molecule, called PD-L1, binds to PD-1, the

T cell dies or becomes docile

� This is a way that the body regulates the immune system,

to avoid an overreaction.

� Since many cancer cells make PD-L1, the cancer cells

can disarm the T cells and inhibit them from attacking

the tumor

PD1/PD-L1 inhibition

Anti-PD-1 and Anti-PDL-1

� Many molecules currently in

clinical trials

� Impressive results in kidney

cancer, melanoma and most

importantly LUNG cancer

� Combination with Anti-CTLA4

lead to a rapid and significant

shrinkage of melanoma tumors in

more than third of the patients

� First approval is expected in 2014

Immunotherapy Made Simple

Natural Hx of Prostate CA

Provenge Infusion

Sipuleucel-T manufacturing

Provenge Safety

� No evidence of increased incidence of autoimmune events

� No evidence of increased incidence of secondarymalignancies

� No deaths attributed to product, as reported bystudy Investigators

Provenge Side Effects

� Most frequent events associated with product infusion: chills and pyrexia

� Generally mild to moderate in severity

� Majority resolved within 24 hours

� < 3% of patients unable to receive all 3 infusionsdue to treatment-related adverse events

� Increased survival by 4 months on average

� Survival improved by up to a year when used in early stage

� FDA approval in 2012

Provenge Benefits

Where do we go from here

� Immunotherapy marks an entirely different way of

treating cancer—by targeting the immune system, not

the tumor itself.

� The field hums with stories of lives extended: the woman

with a grapefruit-size tumor in her lung from

melanoma, alive and healthy 13 years later; the 6-year-

old near death from leukemia, now in third grade and in

remission; the man with metastatic kidney cancer whose

disease continued fading away even after treatment

stopped.

� A corner has been turned and we won't be going back!

THANK YOU