Table 1.
Frequency of common genetic alterations in advanced non-small-cell lung cancer (NSCLC), their clinico-pathologic correlates and the drugs targeting them
| Genetic alteration | Gene | Frequency (%) | Major clinico-pathological correlates | Selected drugs targeting the gene/s (additional targets) (phase of clinical trial evaluation in NSCLC) |
|---|---|---|---|---|
| Mutation | EGFR | 10–35 | Asian, female, never smoker, adenocarcinoma | Erlotinib (approved) |
| Gefitinib (approved) | ||||
| Afatinib (EGFR/HER2) (phase III) | ||||
| Dacomitinib (Pan HER) (phase III) | ||||
| HER2 | 2–4 | Never smoker, female, adenocarcinoma | Lapatinib (EGFR/HER2) (phase III) | |
| Dacomitinib (Pan HER) (phase III) | ||||
| Afatinib (EGFR/HER2) (phase III) | ||||
| PI3K | 1–3 | Squamous cell carcinoma | BKM120 (phase II)Pictilisib (phase II) | |
| PX866 (phase II) | ||||
| XL147 (phase II) | ||||
| XL765 (PI3K/MTOR) (phase II) | ||||
| BEZ235 (PI3K/MTOR) (phase II) | ||||
| BYL719 (phase II) | ||||
| Perifosine (PI3K/AKT) (phase II) | ||||
| PF04691502 (phase II) | ||||
| PKI587 (PI3K/MTOR) (phase I) | ||||
| AKT1 | 1–2 | Not described | MK2206 (phase I) | |
| KRAS | 15–25 | Former/current smokers | None | |
| BRAF | 2–3 | Former/current smokers | Pazopanib (multiple kinases) (phase III) | |
| Dabrafenib (phase II) | ||||
| MEK | 1 | Adenocarcinoma | Selumetinib (phase II) | |
| Trametinib (phase II) | ||||
| DDR2 | Squamous cell carcinoma | Dasatinib (multiple kinases) (phase II) | ||
| Translocation | ALK | 3–7 | Younger age, never/light-smokers, adenocarcinoma | Crizotinib (MET/ALK/ROS) (approved) |
| AP26113 (ALK/EGFR) (phase II) | ||||
| LDK 378 (phase 1) | ||||
| ROS1 | 1 | Younger age, never/light smokers, adenocarcinoma | Crizotinib (MET/ALK/ROS) (phase II) | |
| KIF5B-RET | 1 | Younger age, never/light-smokers, adenocarcinoma | Sunitinib (multiple kinases) (not in clinical trials) | |
| Amplification | MET | 3 | EGFR mutant tumors following prior treatment with EGFR TKI | Onartuzumab (phase III) |
| Tivantinib (phase III)Cabozantinib (multiple kinases) (phase II) | ||||
| FGFR1 | 2 | Squamous cell carcinoma | Lenvatinib (multiple kinases) (phase II) | |
| brivanib alaninate (multiple kinases) (phase II) | ||||
| BGJ398 (pan-FGFR) (phase I) |
NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor.