Table 1.

Characteristics of NSCLC patients examined with acquired resistance to single-agent gefitinib or erlotinib

CaseSexSmokingDrugDuration (mo)Prior chemoPrior RTTumor sites examinedPrimary mutationSecondary mutation
1MNeverG13YYLungdel L747-S752T790M
2MOligoG11YYOmentumdel E746-A750T790M
3FNeverG15YNLung, pericardial fluiddel L747-P753insST790M
4FNeverE10NNPleural fluiddel E746-T751insAT790M
5FOligo→E*n/aYNLungdel E746-A750T790M
9FOligoG19YNAscitesdel E746-A750None
10FNeverG8NNPleuradel E746-A750None
11FNeverE10YNLungdel E746-A750None
12MNeverE9NNPleural fluiddel E746-A750None
14MFormerG12YYInguinal lymph nodedelNone
16MNeverG→E19YYPleural fluidL858RNone
  • NOTE: Smoking, smoking history; never, smoked <100 cigarettes in a lifetime; oligo, smoked 100 or more cigarettes but <15 pack-years total; former, smoked >15 pack-years and quit <1 year before diagnosis of lung cancer. Drug, gefitinib (G) or erlotinib (E). Duration, months on drug until documented progression. Prior chemo, patient did (Y) or did not (N) receive prior systemic chemotherapy. Prior RT, patient did (Y) or did not (N) receive prior radiation therapy to non-CNS sites. Mutation, amino acids affected in EGFR; primary indicates drug-sensitive mutation; del, exon 19 deletion; secondary indicates drug-resistant mutation. For all tumor specimens, exons 18 to 24 of EGFR, which encode the tyrosine kinase domain, were examined by direct Sanger sequencing; DNA was additionally examined for exon 19 deletions and the L858R and T790M missense mutations by more sensitive PCR-RFLP assays. None, no mutation observed.

  • * Patient was initially on a clinical trial involving ZD6474 versus gefitinib for nearly 12 months; following disease progression, she received erlotinib for another 6 months until further disease progression.

  • Mutation analysis reported by Genzyme Genetics.

  • Mutation detected by PCR-RFLP only.