4/13/2018

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Immunotherapy for the lung cancer patient

Feras Abdul-Khalek, MD

Objectives

• Discuss tumor immunology and the mechanisms of action for immunotherapy drugs:– PD-1/PDL-1 inhibitors

• Summary of clinical indications in lung cancer

• Identify the adverse effects associated with immunotherapy drugs

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Global Overview

Global Overview

Global Overview

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Global Overview

Redefining Cancer

• Personalized medicine

– Genetics (CMS and FDA approval for Next Gen Sequencing)

– Biomarkers (they are predictive, are they prognostic?)

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PD-1/PDL-1 inhibitors in market

• Nivolumab (PD-1) - CHECKMATE

• Pembrolizumab (PD-1) - KEYNOTE

• Atezolizumab (PDL-1) - IMpower

• Avelumab (PDL-1) – JAVELIN

• Durvalumab (PDL-1)

– Oceans (atlantic, pacific)

– Planets (Neptune, etc)

– Birds (condor, eagle)

– Nature (danube, alps)

Immunotherapy: T cell kills a cancer cell

cytotoxic T cell

cancer cell

Two parts of the immune system

Innate immune system: First line of defense

Adaptive immune system: specialized/memory

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The two parts of immune attack

Akira S et al. Philo Trans R Soc Lond B Biol Sci. 2011

Immunity in tumor control

Tumor

Mellman I et al. Nature 2011

T cell regulation

Turning up the activating

Blocking the inhibiting (checkpoints)

Mellman I et al. Nature 2011

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Programmed Cell Death 1 (PD-1)

Postow M et al. JCO 2015

Types of immunotherapies

Vaccines

Cytokines

Adoptive T-Cell therapy / Chimeric antigen receptor T-cells

Immunoregulatoryantibodies

“Chemo-immuno-radio” therapy

Ribas A et al. JCO 2013

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Lung cancer - NSCLC

Lung cancer - NSCLC

CA209-003

Which lung cancer patients get immunotherapy?

• Stage III patients after chemoXRT

• Stage IV patients – 2nd line: all

– 1st line: some, and according to PDL-1 status

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Stage III lung cancer - NSCLC

Stage III unresectable

NSCLCNo previous

immunotherapy

Concurrent chemoXRT (≥

2 cycles of platinum-

based chemo)

CT scan shows no

progression

Durvalumab (q2 weeks)x 1 year

placebo

Stage III lung cancer - NSCLC

PACIFIC trial

2nd line treatment

• Nivolumab

• Pembrolizumab

• Atezolizumab

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2nd line treatment

NIVO beat chemo

CHECKMATE – 017 - squamous

KEYNOTE - 010

Pembro beat chemo

1st line treatment

• Pembrolizumab

• 2 trials:– Chemo versus pembro (adenoCa, PDL1 >

50%)

– Chemo/pembro versus chemo

1st line treatment

KEYNOTE 024 - adenoCa

Pembro beat chemo

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1st line treatment

KEYNOTE 021 – phase 2

Pembro + chemo beat chemo

Unconventional response patterns

• Early response

• Stable disease followed by slow, steady decline in tumor burden

• Response after initial increase in total tumor burden (pseudoprogression)

RESPONSE

Nishino M et al. Eur J Radiol 2015

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Immune-related adverse events (ir-AEs)

Immune-related adverse events (ir-AEs)

Pneumonitis

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General management strategies for irAEs

Take home points

• Immunotherapy indications in lung cancer steadily increasing / more patients being treated

• Immune therapies improving survival in lung cancer

• Well tolerated in general, but have their own side effects

• Strong clinical judgement required to manage irAEs

• ED and primary care physicians play a crucial role in managing irAEs