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Non-Small Cell Lung Cancer Genetic Predictors. Sacha Rothschild, MD PhD Medical Oncology. The genomic evolution of lung adenocarcinoma. Pao et al. Lancet Oncol 2011; Pao and Hutchinson. Nat Med 2012.

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non small cell lung cancer genetic predictors

Non-Small Cell Lung CancerGenetic Predictors

Sacha Rothschild, MD PhD

Medical Oncology

the genomic evolution of lung adenocarcinoma
The genomicevolutionoflungadenocarcinoma

Pao et al. Lancet Oncol 2011; Pao and Hutchinson. Nat Med 2012

NSCLC Symposium St. Gallen - Genetic Predictors

survival of patients with oncogenic drivers targeted therapy vs no targeted therapy
Survival of patients with oncogenic drivers – targeted therapy vs. no targeted therapy

Kris et al. Abstract PL03-07

NSCLC Symposium St. Gallen - Genetic Predictors

mutations in the egfr tyrosine kinase domain
Mutations in the EGFR tyrosine kinase domain

Pao W, et al. PNAS 2004; Paez J, et al. Science 2004

NSCLC Symposium St. Gallen - Genetic Predictors

egfr tkis vs chemotherapy as first line therapy
EGFR-TKIs vs. Chemotherapy as first-line therapy

7 randomizedtrialsconfirmingtheroleoffirst-line EGFR-TKI in patientswith EGFR-mutatedadenocarcinoma

1Mok et al. NEJM 2009; 2Lee et al. WCLC 2009; 3Mitsudomi et al. Lancet Oncol 2010; 4Maemondo et al. NEJM 2010; 5Zhou et al. ESMO 2010; 6Rosell et al. Lancet Oncol 2012; 7Yang et al. ASCO 2012; abstract LBA7500

NSCLC Symposium St. Gallen - Genetic Predictors

mechanisms of resistance to egfr kinase inhibitors in egfr mutant nsclc
Mechanismsof Resistance to EGFR kinaseinhibitors in EGFR mutant NSCLC

Yu HA, et al. Clin Cancer Res 2013;19:2240-7

NSCLC Symposium St. Gallen - Genetic Predictors

eml4 alk translocations in nsclc
EML4-ALK translocations in NSCLC
  • EML4-ALK frequency: ~ 4%
  • Primarily in adenocarcinoma
  • More common in younger patients
  • More common in never-smokers

Soda M et al. Nature 2007; 448:561-566.Koivunen et al. CCR 2008

NSCLC Symposium St. Gallen - Genetic Predictors

profile 1007 pfs by independent radiologic review
PROFILE 1007 – PFS by independent radiologic review

Median PFS: 7.7 vs. 3.0 months

Shaw AT, et al. NEJM 2013;368:2385-94

NSCLC Symposium St. Gallen - Genetic Predictors

alk inhibitor resistance mechanisms in alk positive nsclc
ALK-inhibitor resistance mechanisms in ALK-positive NSCLC

Doebele RC, et al. ClinCancer Res 2012;18:1472-82; Shaw AT, et al. ASCO 2013; abstract 8010

NSCLC Symposium St. Gallen - Genetic Predictors

slide10
ROS1
  • Receptortyrosinekinaseoftheinsulinreceptorfamily
  • 1-2% oflungadenocarcinomaspecimensharbor ROS1 fusionabnormality
  • More common in never-smokersand Asian patients
  • ROS1 fusionwiththetransmembranesolutecarrierprotein SLC34A2 results in a constitutivekinaseactivity in a NSCLC cellline

Rikova, et al. Cell 2007; Takeuchi, et a. Nat Med 2011;

Bergethon, et al. JCO 2012; Oxnard et al. J ClinOncol 2013

NSCLC Symposium St. Gallen - Genetic Predictors

crizotinib in ros1 positive nsclc a phase ii study
Crizotinib in ROS1 positive NSCLC – a phase II study

Ou et al. Abstract O16.07

NSCLC Symposium St. Gallen - Genetic Predictors

ras signalling networks
RAS signallingnetworks

Kamauband Weinberg, Nat Rev 2008

NSCLC Symposium St. Gallen - Genetic Predictors

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