Table 1. Types, frequency and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity of EGFR kinase domain mutations in lung cancer.
| EGFR mutation | Approximate frequency (%) | EGFR TKI [in vitro sensitivity and expected overall response rate (ORR)] | ||
|---|---|---|---|---|
| EGFR TKI sensitivity type | 1st generation | 2nd generation | 3rd generation | |
| Gefitinib 250 mg Erlotinib 150 mg |
Afatinib 40 mg | Osimertinib 80 mg | ||
| Sensitizing | ||||
| Exon 19 deletion | 45.0 | ++++ (ORR >70%) | ++++ (ORR >75%) | ++++ (ORR >70%) |
| L858R | 35.0 | ++++ (ORR >60%) | ++++ (ORR >70%) | ++++ (ORR >60%) |
| G719X | 3.0 | ++ (ORR >55%) | +++ (ORR >65%) | ++ (ORR ?) |
| L861Q | 3.0 | ++ (ORR >55%) | ++ (ORR >55%) | ++ (ORR ?) |
| S768I | <1.5 | + (ORR >45%) | ++ (ORR >55%) | ? (ORR ?) |
| Exon 18 indel/E709X | <0.5 | ++ (ORR >55%) | +++ (ORR >65%) | ++ (ORR ?) |
| Exon 19 insertion | <0.5 | ++ (ORR >55%) | ++ (ORR ?) | ++ (ORR ?) |
| A763_Y764insFQEA | <0.5 | ++ (ORR >55%) | ++ (ORR ?) | ++ (ORR ?) |
| Exon 18–25 duplication (EGFR-KDD) | <0.5 | ++ (ORR >55%) | +++ (ORR >65%) | ++ (ORR ?) |
| Rearrangement (EGFR-RAD51) | <0.5 | ++ (ORR >55%) | +++ (ORR ?) | ++ (ORR ?) |
| Insensitizing | ||||
| Exon 20 insertion | >7.0 | – (ORR <5%) | – (ORR <10%) | – (ORR ?) |
| T790M inherited | <1.0 | – (ORR ~0%) | – (ORR ~0%) | ++++ (ORR >60%) |
| Others | >2.0 | ? (ORR ?) | ? (ORR ?) | ? (ORR ?) |
| Acquired resistance | ||||
| T790M + sens. | >50.0 (1st/2nd gen. TKI) | – (ORR ~0%) | – (ORR <5%) | ++++ (ORR >60%) |
| C797X + T790M + sens. | <50.0 (osimertinib) | – (ORR ~0%) | – (ORR ~0%) | – (ORR ~0%) |
++++, maximum inhibition; +++, moderate inhibition; ++, adequate inhibition; +, minimal inhibition; –, no significant inhibition beyond the therapeutic window of wild-type EGFR; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; ?, unknown; sens, sensitizing mutation; gen., generation.