Table 1

Thirty-seven paired lung tumor biopsies resistant to EGFR inhibitors. EGFR, epidermal growth factor receptor; amp, amplification; del, deletion; Adeno, adenocarcinoma; Adenosquam, adenosquamous; NSCLC, non–small cell lung cancer not otherwise specified; SCLC, small cell lung cancer; CA, carcinoma; EMT, epithelial to mesenchymal transition; TKI, tyrosine kinase inhibitor; Erlo, erlotinib; Gef, gefitinib.

ID#AgeSexEGFR mutationBaseline histologySummary of changesPrimary TKI (time on TKI)TKI status at repeat biopsy
T790M
166ML858RAdenoT790MErlo (6 months)Off (2 months)
274FExon 19 delAdenoT790MErlo (12 months)On
347FExon 19 delAdenoT790MGef (15 months)On
460FExon 19 delAdenoT790MErlo (7 months)On
557ML858RAdenoT790MGef (5+ years)On
647MExon 19 delAdenoT790MErlo (12 months)Off (14 months)
758FExon 19 delAdenoT790MErlo (3+ years)On
869ML858RAdenoT790M*Erlo (2 years)On
958FG719C, S768IAdenoT790MErlo (2+ years)On
1046FExon 19 delAdenoT790MErlo (3 years)Off (3 months)
1153FExon 19 delAdenoT790MErlo (16 months)On
1259FL858RAdenoT790MErlo (8 months)Off (5 months)
T790M + EGFR amp
1342MExon 19 delAdenoT790M, EGFR ampErlo (5 months)On
1455MExon 19 delAdenoT790M, EGFR ampErlo (10 months)On
1537FExon 19 delAdenoT790M, EGFR ampErlo (6 months)On
T790M + new, additional mutations
1688FExon 19 delAdenoT790M, β-cateninErlo (2+ years)On
1785MExon 19 delAdenoT790M, β-cateninErlo (22 months)On
1875FExon 19 delAdenoT790M, APCErlo (18 months)On
MET amplification
1961ML858RAdenosquamMET amp, loss EGFR ampErlo (15 months)On
2076ML858RAdenoMET ampErlo (13 months)Off (5 months)
Acquired PIK3CA mutation
2165MExon 19 delAdenoPIK3CA acquisitionErlo (21 months)On
Histologic transformation (one with acquired PIK3CA mutation)
2267FL858RAdenoSCLC transformationErlo (22 months)On
2354FExon 19 delAdenoSCLC transformationErlo (3+ years)On
2456FL858RAdenoSCLC transformation, PIK3CAErlo (14 months)On
2540FExon 19 delAdenoSCLC transformationErlo (2+ years)Off (2 months)
2661FL858RAdenoSCLC transformationErlo (18 months)On
2766ML858RAdenoEMTErlo (11 months)On
2859MExon 20 insAdenoEMTGef (11 months)On
2964ML858RAdenoSarcomatoid CA, loss of β-cateninErlo (11 months)Off (2 weeks)
No histological or genetic changes identified
3062FL858RAdenoNoneErlo (6 months)On
3152FExon 19 delAdenoNoneGef (17 months)On
3258FExon 19 delAdenoNoneErlo (14 months)On
3361FL858RAdenoNoneErlo (13 months)On
3485FExon 19 delAdenoNoneErlo (6 months)On
3562ML858RNSCLCNoneGef (3+ years)On
3656ML858RAdenoNoneErlo (5 months)Off (<2 weeks)
3751FExon 19 delAdenoNoneErlo (8 months)On

*TP53 mutation suspected to be present, but not confirmed.

APC mutation confirmed in resistant specimen, but not confirmed to be present in initial biopsy.

Exon 20 insertion assay added to SNaPshot for this patient given direct sequencing result from pretreatment sample.