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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 therapy vs.

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 therapy vs.

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
Mechanisms therapy vs. of 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 therapy vs.

  • 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 therapy vs.

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 therapy vs.

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

NSCLC Symposium St. Gallen - Genetic Predictors


ROS1 therapy vs.

  • 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 therapy vs. phase II study

Ou et al. Abstract O16.07

NSCLC Symposium St. Gallen - Genetic Predictors


Ras signalling networks
RAS therapy vs. signallingnetworks

Kamauband Weinberg, Nat Rev 2008

NSCLC Symposium St. Gallen - Genetic Predictors


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