Biology of EGFR Mutations and Acquired Resistance to EGFR TKIs

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  • Biology of EGFR Mutations and Acquired Resistance to EGFR TKIsThomas J. Lynch, Jr., M.D.Director, Yale Cancer CenterPhysician-in-Chief, Smilow Cancer Hospital

  • Cancer Paradigm 2011

  • Epidermal Growth Factor Receptor Mutations

  • Study design

    *Never smokers,

  • Objective response rate in EGFR mutation positive and negative patientsGefitinib Carboplatin / paclitaxel

    EGFR M+ odds ratio (95% CI) = 2.75 (1.65, 4.60), p = 0.0001

    EGFR M- odds ratio (95% CI) = 0.04 (0.01, 0.27), p = 0.0013

    Overall response rate (%)(n = 132)(n = 129)(n = 91)(n = 85)Odds ratio >1 implies greater chance of response on gefitinib71.2%47.3%1.1%23.5%Mok TS et al. ESMO 2008;LBA2.

  • Progression-free survival in EGFR mutation positive and negative patientsMok TS et al. ESMO 2008;LBA2.

    Progression-free survival eventsGefitinibCarboplatin + paclitaxelHazard ratio (95% CI) p-valueEGFR mutation-positive (n = 132; 129) 73.5% 86.0% 0.48 (0.36-0.64)

  • Response to treatment in the intention-to-treat population, according to treatment group*Maemondo M et al. N Engl J Med 2010;362:2380-2388.

  • Maemondo M et al. N Engl J Med 2010;362:2380-2388.Progression-free survival among the study patientsMedian PFSGefitinib (n = 114), 10.8 monthsCarboplatin/paclitaxel (n = 110), 5.4 months Hazard ratio 0.30 p-value < 0.001

  • Maemondo M et al. N Engl J Med 2010;362:2380-2388.Overall survival among the study patientsMedian survivalGefitinib (n = 114), 30.5 monthsCarboplatin/paclitaxel (n = 114), 23.6 months Hazard ratio not reported p-value = 0.31

  • Resistance mechanisms in EGFR mutant NSCLC

  • Regales et al. JCI 2009Combination of BIBW2992 and cetuximab is effective against EGFR T790M"The combination of both agents together induced dramatic shrinkage of erlotinib-resistant tumors harboring the T790M mutation, because together they efficiently depleted both phosphorylated and total EGFR."

  • Research To Practice could not obtain permission to reproduce this slide at the time of publication. To access the following abstract, please visit our Select Publications page: Horn L et al. Proc IASLC 2011;Abstract O19.07.

  • Saturday, February 11, 2012Hollywood, FloridaFaculty Co-ChairsRogerio C Lilenbaum, MDMark A Socinski, MDCo-Chair and ModeratorNeil Love, MDChandra P Belani, MDJohn Heymach, MD, PhDPasi A Jnne, MD, PhDThomas J Lynch Jr, MDHeather Wakelee, MD

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