EGFR Mutations in US Hispanics

with Lung Adenocarcinoma

Jonathan Villena-Vargas, M.D.

Department of Cardiothoracic Surgery, Weill Cornell Medicine,

New York-Presbyterian Hospital

Kadmon/Sanofi

Disclosure

1. Background on early-stage non-small cell lung cancer

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2) Current advances in treatment

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3) Mutational analysis and prognosis in Latinos

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4) Future directions

Outline

The most common cause of cancer-related deaths, with over 1.8 million annual deaths expected globally.

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NSCLC accounts for 85% of all lung cancers.

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Treatment has altered dramatically, primarily due to targeted and immunotherapy-based treatments.

Background

W.H.O 2018

Herbst et al Nature 2018

Targeted therapy in non-small cell lung cancer

Wang et al Nature Medicine 2021

Actionable mutations in NSCLC

-Adenocarcinoma 38%

-Squamous carcinoma ~1%

Targeted therapy in non-small cell lung cancer

Wang et al Nature Medicine 2021

Targeted therapy in advanced NSCLC

Targeted therapy in non-small cell lung cancer

Targeted therapy in advanced NSCLC

Targeted therapy in resectable EGFR+ NSCLC

Wu Yi et al NEJM 2020

Wang et al Nature Medicine 2021

Cancer discovery 2021

Cancer discovery 2021

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• Activating mutations in EGFR occur in 40-60% of Asian,15% of Black patients and 15-20% of White patients with lung adenocarcinoma (1)
• Prevalence of the mutation in 60 million U.S Hispanic patients with lung adenocarcinoma has not been well described (2)

Lee et al. J Thorac Oncol. 2017

Pew Research Center. 2017

Methods

• Queried our prospective database (2015-2019) for patients undergoing resection for lung adenocarcinoma
• Patients undergoing resection for lung adenocarcinoma were assessed for EGFR mutations (exons 18-21) utilizing a targeted gene panel
• Patients were stratified by self-identified race/ethnicity; patients were exclude if race/ethnicity was unknown
• Demographics were compared using Chi-Squared analysis and survival with Kaplan-Meier Curves

Villena-Vargas, Weill Cornell Medicine, USA

Results

1035 patients were identified from 2015-2019 that underwent resection for lung cancer in our database

1035 lung cancer resections identified

768 patients with adenocarcinoma histology

668 patients with known self-identified race/ethnicity

267 patients with non-adenocarcinoma histology

100 patients race/ethnicity was unknown

Villena-Vargas, Weill Cornell Medicine, USA

• Hispanic patients displayed a higher frequency of EGFR mutations than Whites (35% vs. 20%, p=0.013)

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• Hispanic and Asian patients were younger and less likely to be smokers than White patients (59% & 45% vs. 82%, p<0.001).

Results

Villena-Vargas, Weill Cornell Medicine, USA

• Hispanic EGFR mutant patients had worse 3-year overall survival (OS) than White and Asian patients

Results

Villena-Vargas, Weill Cornell Medicine, USA

• Hispanic EGFR mutant patients had worse 3-year overall survival (OS) than White and Asian patients

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• EGFR mutations were similar across groups

Results

Villena-Vargas, Weill Cornell Medicine, USA

Clinically matched Latino and NHW with NSCLC adenocarcinoma

RNA

Bulk RNAseq

New Englander precision medicine

DNA

Immunophenotyping- Transcriptome deconvolution

Whole genome sequencing

Future directions

Mittal Lab

Dr. Vivek Mittal

Tatiana Cruz

Arshdeep Singh

Geoffrey Markowitz

Shelley Bai

Mitchell Martin

Lab members

McGraw Lab

Dr. Timothy McGraw

Lab members

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Funding

Kadmon/Sanofi

Mastercard pilot grant

Dean’s Award Cornell University

GMaP/NIH Stimulus Award

CT Surgery Department

Dr. Altorki

Thoracic Surgery Faculty

Neuberger Berman Lung Cancer Research Center

Dr. Altorki

Dr. Vivek Mittal

Murtaza Malbari

Acknowledgements

Jonathan Villena-Vargas

Thoracic Surgery

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jov9069@med.cornell.edu

Gracias y cuidence!

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PRIOR EXPOSURE TO NON-STEROIDAL ANTI-INFLAMMATORY DRUGS REDUCES RATE OF ORGAN FAILURE AND IN-HOSPITAL MORTALITY IN ACUTE PANCREATITIS

Antonio Mendoza Ladd MD, AGAF, FACG, FASGE

Associate Professor of Medicine

Medical Director of Endoscopy

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BACKGROUND

• Pro-inflammatory cytokines play a key role in the development of organ failure (OF) and mortality in patients with acute pancreatitis (AP).

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• NSAIDs have been linked to a lower expression of such cytokines in animals and recently in humans. However, it is unclear if this improves immediate clinical outcomes.

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• The aim of this study was to determine if prior NSAID exposure decreases the rates of OF and in-hospital mortality in humans with AP.

METHODS

• Retrospective cohort of medical records of adult patients admitted with AP using a national Veterans Administration database.

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• NSAID use was determined through pharmacy claims.

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• duration of use was divided into ≤1 year (≥1 day but < 1 year) or >1 year.

NSAIDS ANALYZED

• mefenamic acid
• meclofenamate
• ketoprofen
• indomethacin
• fenoprofen
• piroxicam
• etodolac
• naproxen
• diclofenac sodium
• oxaprozin

• naproxen sodium
• diclofenac potassium
• flurbiprofen
• ibuprofen
• Diclofenac
• celecoxib
• tolmetin
• ketorolac
• nabumetone
• meloxicam
• sulindac

METHODS

• two groups: prior NSAID use (AP+NSAID); no prior nsaid use (AP-NSAID).

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• Cases identified using AP ICD 9 diagnosis code 577.0. Cases divided into gallstone and non-gallstone related.

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• OF defined by documentation of: acute kidney injury(584.9), respiratory failure (518.81) and cardiovascular failure (458.9).

METHODS

• Comparison between the two groups done using univariate and multivariate analysis.

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• Inclusion criteria: any patient admitted with ap who filled a ≥30 day prescription for NSAIDs up to the day prior to admission.

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• Exclusion criteria: patients who filled a ≥30 day prescription for NSAIDs for the first time after admission.

PATIENT SELECTION PROCESS

RESULTS

• Median age 60 years, 68% were Caucasian, 95% were males and ~2% died during the hospitalization.

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• DM, smoking and ETOH consumption were significantly higher in the AP+NSAID group.

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• age, gallstone etiology, rate of ERCP and pancreatic cancer were significantly higher in the AP –NSAID one.

SIGNIFICANT DIFFERENCES IN THE 2 GROUPS

MULTIVARIATE ANALYSIS OF OUTCOMES

MULTIVARIATE ANALYSIS OF OUTCOMES BY NSAID USE DURATION

MULTIVARIATE ANALYSIS OF OUTCOMES BY NSAID DURATION

CONCLUSION

• Prior use of NSAIDs for as short as ≥1 day prior to AP onset is associated with a lower incidence of OF and in-hospital mortality in adult patients.

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• The role of NSAIDs as therapeutic agents in AP should be evaluated in clinical trials.

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Richard Aguilar, MD.

Chief Clinical Officer, Cano Health

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IMPROVING EGFR VALUES IN A REAL-WORLD PATIENT COHORT. SLOWED PROGRESSION OF STAGE 3 CKD FROM A TWO-YEAR ANALYSIS OF 1,528 ELDERLY LATINO PATIENTS IN A MEDICARE ADVANTAGE POPULATION.

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NHMA 25th Annual Conference,

Crystal City, VA

March 24 – 27, 2022

Disclosure:

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Speakers Bureau for Novo Nordisk A/S

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Patients with

Diabetes and CKD

https://www.cghjournal.org/article/S1542-3565(19)30839-0/fulltext

CKD Stage 3

Albuminuria >300mg/mmol

*Afkarian M et al. J Am Soc Nephrol. 2013;24(2):302-308

Pts with CKD have significantly ↑ associated cost of care

• increased need for medications, clinic/clinician visits
• hospitalization, cardiovascular complications
• myocardial infarction, stroke, congestive heart failure
• costs of dialysis or kidney transplant.

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Pts with DM and CKD, the ten-year standardized for

all-cause mortality is*:

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• 4X (7.7% vs 31.1%) and cardiovascular mortality
• 6X (3.4% vs 19.6%) that of pts without DM and CKD.

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https://nccd.cdc.gov/ckd/detail.aspx?QNum=Q601&Strat=Age,%20Race/Ethnicity 2020

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25% Patients 70+ Y/O have CKD Stage 3-5

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National Health and Nutrition Examination Survey

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• Suggest that CKD prevalence is 38%
• Those > 65 years old
• Compared with 13% in the overall US population

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Coresh et al. JAMA 2007

>80% of CanoHealth patients are Latino and have higher rates of chronic diseases when compared with average US Medicare Advantage patients:

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• Hypertension (84% vs 70%)
• Diabetes (41% vs 33%)
• CKD (45% vs 38%).

The CREDENCE trial showed that canagliflozin is superior to placebo in improving glycemic control and reducing adverse renal events among patients with DM2 and established CKD

June 13, 2019�N Engl J Med 2019; 380:2295-230

The FDA approved a new indication for the SGLT2 inhibitor canagliflozin to 

reduce the risk for end-stage renal disease Sept 2019

PBO: eGFR reduction ≈ 5 ml/min/1.73m² per Year

• On January 1, 2018 through December 31^st 2018,

2,307 elderly patients (≥65 YO) were enrolled in CanoHealth’s

staff model. 

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• In current study, we identified and analyzed 1,527 of those patients with comorbid diabetes and CKD Stage 3 (along with albuminuria between 300- 5,000 mg) (average age = 75 YO) upon intake into CanoHealth, or within 3 months of the patient enrollment date.

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• eGFR values were collected (quarterly or half-yearly) for 24 months. Alc, Body Mass Index (BMI) and blood pressure were collected at baseline and end of study.

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• Upon receiving intensive management in line with the CanoHealth care model.

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• Change in eGFR from baseline at 6, 12, 18 and 24 months were +2.4, +1.8, +0.6, and – 1.1 ml/min/1.73 m², respectively.

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Example of tools embedded

in the EHR Platform, Structured Data

• Average 11 visits per year
• Pharmacy Compliance (5 STAR HTN, Chol, OAD)
• Cano at Home
• 100% NCQA Certification, DRP & Heart/Stroke Prev
• TEACH Program- telehealth post discharge management
• Pop Health- Risk Stratify
• In House Billing and Coding dept

Example of tools:

That contribute to patient care

• CKD has wide ranging health effects
• The elevation of CKD with a new Risk Adjustment Factor by CMS
• Highlighting the importance related to increase in health care services and costs to managing it and its complications.

Thank our Clinical Operations (clinical staff), Care Management, and Pharmacy teams who worked to diagnose, treat, manage, and collect the data for this poster presentation.

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Special thanks to:

Lina, Silka, Michelle, Morgan, and Stephany

Questions…

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