Characteristics of NSCLC patients examined with acquired resistance to single-agent gefitinib or erlotinib
| Case | Sex | Smoking | Drug | Duration (mo) | Prior chemo | Prior RT | Tumor sites examined | Primary mutation | Secondary mutation |
|---|---|---|---|---|---|---|---|---|---|
| 1 | M | Never | G | 13 | Y | Y | Lung | del L747-S752 | T790M |
| 2 | M | Oligo | G | 11 | Y | Y | Omentum | del E746-A750 | T790M |
| 3 | F | Never | G | 15 | Y | N | Lung, pericardial fluid | del L747-P753insS | T790M |
| 4 | F | Never | E | 10 | N | N | Pleural fluid | del E746-T751insA | T790M |
| 5 | F | Oligo | →E* | n/a | Y | N | Lung | del E746-A750 | T790M† |
| 6 | F | Never | G | 15 | N | N | Lung | L858R | T790M |
| 7 | F | Never | G | 13 | N | N | Lung | L858R | T790M‡ |
| 8 | F | Never | G | 13 | Y | Y | Brain | L858R | D761Y |
| 9 | F | Oligo | G | 19 | Y | N | Ascites | del E746-A750 | None |
| 10 | F | Never | G | 8 | N | N | Pleura | del E746-A750 | None |
| 11 | F | Never | E | 10 | Y | N | Lung | del E746-A750 | None |
| 12 | M | Never | E | 9 | N | N | Pleural fluid | del E746-A750 | None |
| 13 | F | Oligo | G | 7 | Y | N | Cervix | del‡ | None |
| 14 | M | Former | G | 12 | Y | Y | Inguinal lymph node | del‡ | None |
| 15 | F | Oligo | G | 28 | N | N | Lung | del‡ | None |
| 16 | M | Never | G→E | 19 | Y | Y | Pleural fluid | L858R | None |
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.