1. Lung cancer Treatment Consequences of the Lack of Patients of color & Structural barriers to Quality
Christopher S. Lathan, M.D., M.S., M.P.H. Assistant Professor of Medicine
Faculty Director of Cancer Care Equity, Dana-Farber Cancer Institute

2. Overview Race/SES Disparities in lung cancer
Targeted therapy in Lung Cancer
Treatment equity 2

3. Disparities Framework
Kawaga-Singer CA, 2010

4. Male Death Rates for NSCLC
Cancer Facts and Figures for African Americans 2013

5. 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

6. 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 6

7. Targeted Therapy for Lung Cancer7

8. Personalized Medicine

9. 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
After 3 months gefitinib treatment
Before treatment
Slide courtesy of M. Meyerson MD

10. EGFR Timeline ALK Timeline
EGFR mutations identified
2004
1990s
2005
2009
Quinazoline EGFR inhibitors discovered
Gefitinib approved for EGFR mutant NSCLC
Erlotinib approved for NSCLC
2007
2008
EML4-ALK discovered
First EML4-ALK patient treated with ALK inhibitor
2009
Phase III study starts
ALK Timeline
Crizotinib approved for ALK-rearranged NSCLC
2011
Courtesy of Pasi Janne MD

11. Evolution of Identification of Genomic Alterations in Lung Adenocarcinoma
No known genotype
No known genotype
2004
2009
2013
Courtesy of Pasi Janne MD

12. Benefits of understanding racial differences in mutation frequency
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

13. 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

14. Lung cancer Targets Cancer Gene Different Human Populations Caucasians
African Americans
East Asians
*EGFR
10-20%
~10%
30-60%
KRAS
20-30%
MET
C-met
5.3%
~4.5%
13.5%
EML4-ALK
5.6-13% ?
3.7%
Reproduced from Patrick Ma ASCO 2010

15. Genotype Directed Clinical Trials
Gene
Clinical Trial
EGFR
(Erlotinib); (dacomitinib)
ALK
(CH )
KRAS
(selumetinib +/- docetaxel)
BRAF
(GSK )
ERBB2
(dacomitinib); (neratinib +/- temsirolimus)
PIK3CA
(GDC-0980 & chemo)
ROS1
(phase I Crizotinib)
FGFR
(ponatinib)
RET
(sunitinib)
MET
(phase I Crizotinib); (Erlotinib +/- MetMab)

16. BATTLE STUDY Schema for BATTLE study.
Kim E S et al. Cancer Discovery 2011;1:44-53

17. Sequencing Alk and EGFR on all adenocarcinomas
Squamous cells per protocol
ROS, BRAF, HER2 PIK3CA
Secondary Mutations re-biopsy
Immune based therapy is changing practice, Nivolumab, Pembrolizumab and PD-L1 markers are the next frontier.
Christopher S. Lathan MD MS MPH

18. Lynch et al Genet Med 2013
Christopher S. Lathan MD MS MPH

19. Institutions Adopting EGFR assay
H – NCI CC
Ordered EGFR Assay
Lynch et al Genet Med 2013

20. Summary
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