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, tyro-sine kinase inhibitor; Erlo, erlotinib; Gef, gefitinib.
| ID# | Age | Sex | EGFR mutation | Baseline histology | Summary of changes | Primary TKI (time on TKI) | TKI status at repeat biopsy |
|---|---|---|---|---|---|---|---|
| T790M | |||||||
| 1 | 66 | M | L858R | Adeno | T790M | Erlo (6 months) | Off (2 months) |
| 2 | 74 | F | Exon 19 del | Adeno | T790M | Erlo (12 months) | On |
| 3 | 47 | F | Exon 19 del | Adeno | T790M | Gef (15 months) | On |
| 4 | 60 | F | Exon 19 del | Adeno | T790M | Erlo (7 months) | On |
| 5 | 57 | M | L858R | Adeno | T790M | Gef (5+ years) | On |
| 6 | 47 | M | Exon 19 del | Adeno | T790M | Erlo (12 months) | Off (14 months) |
| 7 | 58 | F | Exon 19 del | Adeno | T790M | Erlo (3+ years) | On |
| 8 | 69 | M | L858R | Adeno | T790M* | Erlo (2 years) | On |
| 9 | 58 | F | G719C, S768I | Adeno | T790M | Erlo (2+ years) | On |
| 10 | 46 | F | Exon 19 del | Adeno | T790M | Erlo (3 years) | Off (3 months) |
| 11 | 53 | F | Exon 19 del | Adeno | T790M | Erlo (16 months) | On |
| 12 | 59 | F | L858R | Adeno | T790M | Erlo (8 months) | Off (5 months) |
| T790M + EGFR amp | |||||||
| 13 | 42 | M | Exon 19 del | Adeno | T790M, EGFR amp | Erlo (5 months) | On |
| 14 | 55 | M | Exon 19 del | Adeno | T790M, EGFR amp | Erlo (10 months) | On |
| 15 | 37 | F | Exon 19 del | Adeno | T790M, EGFR amp | Erlo (6 months) | On |
| T790M + new, additional mutations | |||||||
| 16 | 88 | F | Exon 19 del | Adeno | T790M, β-catenin | Erlo (2+ years) | On |
| 17 | 85 | M | Exon 19 del | Adeno | T790M, β-catenin | Erlo (22 months) | On |
| 18 | 75 | F | Exon 19 del | Adeno | T790M, APC† | Erlo (18 months) | On |
| MET amplification | |||||||
| 19 | 61 | M | L858R | Adenosquam | MET amp, loss EGFR amp | Erlo (15 months) | On |
| 20 | 76 | M | L858R | Adeno | MET amp | Erlo (13 months) | Off (5 months) |
| Acquired PIK3CA mutation | |||||||
| 21 | 65 | M | Exon 19 del | Adeno | PIK3CA acquisition | Erlo (21 months) | On |
| Histologic transformation (one with acquired PIK3CA mutation) | |||||||
| 22 | 67 | F | L858R | Adeno | SCLC transformation | Erlo (22 months) | On |
| 23 | 54 | F | Exon 19 del | Adeno | SCLC transformation | Erlo (3+ years) | On |
| 24 | 56 | F | L858R | Adeno | SCLC transformation, PIK3CA | Erlo (14 months) | On |
| 25 | 40 | F | Exon 19 del | Adeno | SCLC transformation | Erlo (2+ years) | Off (2 months) |
| 26 | 61 | F | L858R | Adeno | SCLC transformation | Erlo (18 months) | On |
| 27 | 66 | M | L858R | Adeno | EMT | Erlo (11 months) | On |
| 28 | 59 | M | Exon 20 ins‡ | Adeno | EMT | Gef (11 months) | On |
| 29 | 64 | M | L858R | Adeno | Sarcomatoid CA, loss of β-catenin | Erlo (11 months) | Off (2 weeks) |
| No histological or genetic changes identified | |||||||
| 30 | 62 | F | L858R | Adeno | None | Erlo (6 months) | On |
| 31 | 52 | F | Exon 19 del | Adeno | None | Gef (17 months) | On |
| 32 | 58 | F | Exon 19 del | Adeno | None | Erlo (14 months) | On |
| 33 | 61 | F | L858R | Adeno | None | Erlo (13 months) | On |
| 34 | 85 | F | Exon 19 del | Adeno | None | Erlo (6 months) | On |
| 35 | 62 | M | L858R | NSCLC | None | Gef (3+ years) | On |
| 36 | 56 | M | L858R | Adeno | None | Erlo (5 months) | Off (<2 weeks) |
| 37 | 51 | F | Exon 19 del | Adeno | None | Erlo (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.