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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Biology of EGFR Mutations and Acquired Resistance to EGFR TKIs

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