Lung cancer Treatment - PowerPoint Presentation

Slide1

Lung cancer TreatmentConsequences of the Lack of Patients of color & Structural barriers to Quality

Christopher S. Lathan, M.D., M.S., M.P.H. Assistant Professor of MedicineFaculty Director of Cancer Care Equity, Dana-Farber Cancer Institute

Overview

Race/SES Disparities in lung cancerTargeted therapy in Lung Cancer

Treatment equity

Disparities Framework

Kawaga-Singer

CA, 2010

Male Death Rates for NSCLC

Cancer Facts and Figures for African Americans 2013

NSCLC and Race

The incidence rates and mortality rates of lung cancer are highest in Black men

Over the past 40 years there has been a decrease in lung cancer incidence and mortality in all races

Black men are still more likely to have lung cancer when smoking habits are adjusted for.

Cancer Facts and Figures for African Americans 2013

Lung Cancer and Income

Low income takes on special importance in lung cancer: Double jeopardy phenomenon Low income increased risk due to tobacco Low income increases risk of dying

Income is directly related to stage of disease at presentation

Stage at presentation drives mortality

Albano et al JNCI 2007

Targeted Therapy for Lung Cancer

Personalized Medicine

www.mdanderson.org/.../index.html

Slide courtesy of M. Meyerson MD

EGFR

Four groups of patients showed increased response to gefitinib

(Miller et al., JCO, 2004). Patients with adenocarcinoma. Patients

from Japan (compared to U.S. or Europe)

Women

Non-smokers

Same patient population in whom we found

EGFR

mutations

In Paez, Pao and Lynch reports, 25 of 31 gefitinib responders had

EGFR

mutations—validated in larger studies

Before treatment

After 3 months gefitinib treatment

EGFR Timeline

1990s

Quinazoline EGFR inhibitors discovered

2005

Erlotinib approved for NSCLC

2009

Gefitinib approved for EGFR mutant NSCLC

2004

EGFR mutations identified

2007

2008

EML4-ALK discovered

First EML4-ALK patient treated with ALK inhibitor

2009

Phase III study starts

ALK Timeline

2011

Crizotinib approved for ALK-rearranged NSCLC

Courtesy of Pasi Janne MD

Evolution of Identification of Genomic Alterations in Lung Adenocarcinoma

2009

2004

2013

No known genotype

1984 - 2003

No known genotype

Courtesy of Pasi Janne MD

EGFR mutations in lung adenocarcinoma are much less common in Caucasian (8%) than East Asian (30%) populations—note that these are racial differences in SOMATIC mutations

EGFR mutations are somatic, so racial differences may be due to inherited differences in some other genes, or due to environmental factors (diet, socioeconomic, etc.)

Christopher S. Lathan MD MS MPH

Benefits of understanding racial differences in mutation frequency

Frequencies of EGFR mutations in populations of African descent are not well characterized

Frequencies of other genomically altered therapeutic targets (BRAF, ALK, ERBB2) were completely uncharacterized in African-American and African populations. (recent study)

Christopher S. Lathan MD MS MPH

Benefits of understanding racial differences in mutation frequency

Lung cancer Targets

Cancer Gene

Different Human Populations

Caucasians

African Americans

East Asians

*EGFR

10-20%

~10%

30-60%

KRAS

20-30%

20-30%

20-30%

MET

C-met

5.3%

~4.5%

13.5%

EML4-ALK

5.6-13%

?

3.7%

Reproduced from Patrick Ma ASCO 2010

Gene

Clinical Trial

EGFR

09-210

(Erlotinib); 09-018 (dacomitinib)

ALK

12-075 (CH5424802)

KRAS

12-547

(selumetinib +/- docetaxel)

BRAF

11-023

(GSK2118436)

ERBB2

09-018 (dacomitinib);

13-148 (neratinib +/- temsirolimus)

PIK3CA

10-419

(GDC-0980 & chemo)

ROS1

06-068 (phase

I Crizotinib)

FGFR

12-327 (ponatinib)

RET

13-086 (sunitinib)

MET

06-068 (phase

I Crizotinib); 11-484 (Erlotinib +/- MetMab)

Genotype Directed Clinical Trials

BATTLE STUDY

Kim E S et al. Cancer Discovery 2011;1:44-53

Alk and EGFR on all adenocarcinomasSquamous cells per protocolROS, BRAF, HER2 PIK3CASecondary Mutations re-biopsyImmune based therapy is changing practice, Nivolumab, Pembrolizumab and PD-L1 markers are the next frontier.

Christopher S. Lathan MD MS MPH

Sequencing

Christopher S. Lathan MD MS MPH

Lynch et al Genet Med 2013

Institutions Adopting EGFR assay

H –

NCI CC

Ordered EGFR Assay

Lynch et al Genet Med 2013

Racial/class disparities are multifactorial, and multilevel requiring not only improvements in treatments, but also access resulting in treatment equity.Without a focus on disseminating somatic testing to underserved patients, the technology can exacerbate existing disparities.

Community based efforts : are needed to have representative samples across tissue type.

Christopher S. Lathan MD MS MPH

Summary