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

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

Disparities Framework Kawaga-Singer CA, 2010

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

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 6

Targeted Therapy for Lung Cancer 7

Personalized Medicine www.mdanderson.org/.../index.html

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

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

Evolution of Identification of Genomic Alterations in Lung Adenocarcinoma No known genotype No known genotype 1984 - 2003 2004 2009 2013 Courtesy of Pasi Janne MD

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

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

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

Genotype Directed Clinical Trials 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)

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

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

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

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

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