Table 2. Published or presented studies with results in patients with EGFR mutant lung cancer and acquired resistance to EGFR TKI.
| Target | Agents | Study | Phase | Eligibility | # pts / (% EGFRm+) | RR (%) | PFS (months) |
|---|---|---|---|---|---|---|---|
| 1st/2nd generationEGFR TKI | Neratinib | Ref. 24 | 2 | PR or SD × 3 months on TKI and EGFRm | 91 (100) | 3 | 3.6 |
| XL647 | Ref. 26 | 2 | PR or SD × 3 months on TKI or EGFR T790M | 33 (53) | 3 | 3.5 | |
| Afatinib vs. Placebo | Ref. 23 | 2B/3 | 1-2 lines previous chemo + PD after 3 months on TKI | 585 (16) | 7 (A) <1 (P) |
3.3 1.1 |
|
| Afatinib | Ref. 70 | 2 | PD after 3 months on TKI | 62 (73) | 8 | 4.4 | |
| Dacomitinib | Ref. 25 | 2 | PD after chemo and TKI | 50 (48) | 9 | 4.5 | |
| MM-121 + Erlotinib | Ref. 50 | 1 | Advanced NSCLC | 32 (35) | 3* | 2* | |
| AP26113 | Ref. 33 | 1 | Solid tumor, subset with EGFR T790M+ | 12 T790M+ | 0 | NR | |
| Mutant-specific TKI | CO-1686 | Ref. 35 | 1 | EGFRm and prior TKI | 40 T790M+ (100) | T790M+ 58 | NR |
| AZD9291 | Ref. 37 | 1 | EGFRm + PD on TKI | 107 T790M+ (100) | T790M+ 64 | NR | |
| HM61713 | Ref. 38 | 1 | EGFRm + PD on TKI | 48 T790M+ | T790M+ 29 | 4.4 | |
| EGFR antibodies | Cetuximab + Erlotinib | Ref. 28 | 2 | PR or SD × 3 months on TKI orEGFRm | 19 (84) | 0 | 3 |
| Cetuximab + Afatinib | Ref. 30 | 1B | Jackman criteria | 126 (98) | 29 | 4.7 | |
| Chemotherapy | Carboplatin/Pac litaxel | Ref. 71 | 3 | PD after first-line gefitinib | 52 (100) | 28.8 | NR |
| Chemo/Erlotinib vs. Chemo | Ref. 21 | Retro | Jackman criteria | 78 (100) | 41 (C+E) 18 (C) | 4.4 4.2 |
|
| Pemetrexed + Gefitinib or Erlotinib | Ref. 72 | 2 | EGFRm and PD on TKI | 27 (100) | 25.9 | 7.0 | |
| Chemo/Erlotinib vs. Chemo | Ref. 73 | 2 | PR or SD × 3 months on TKI | 46 (67) | NR | E = 4.6 No E = 5.4 | |
| mTOR | Everolimus + Gefitinib or Erlotinib | Ref. 64 | 2 | PR on TKI or 6 months SD + EGFRm | 13 (62) | 0 | 3 |
| Everolimus | Ref. 74 | 2 | Prior TKI × 1 month | 43 (0) | 2 | 2.7 | |
| HSP90 | IPI-504 | Ref. 75 | 2 | PD on TKI | 28 (100) | 4 | 2.8 |
| AUY-922 + Erlotinib | Ref. 66 | 1/2 | Jackman Criteria | 22 (100) | 16 | NR | |
| AUY-922 | Ref. 65 | 2 | EGFRm and prior EGFR TKI | 35 (100) | 18 | NR | |
| HDAC | Erlotinib + Vorinostat | Ref. 76 | 1/2 | EGFRm after PD on at least 3month TKI | 33 (100) | 0 | 2 |
| MET | INC280 + Gefitinib | Ref. 47 | 1 | EGFRm, MET positive and PD on TKI | 46 (100) | 17 | NR |
| Other | Cabozantinib | Ref. 46 | 2 | EGFRm and PD on TKI | 11 | ||
| Dasatinib + Erlotinib | Ref. 77 | 2 | PR or SD × 6 months on TKI or EGFRm | 12 (100) | 0 (D+E) | 0.9 | |
| Hydroxy-chloroquine +/- Erlotinib | Ref. 78 | 1 | PR or SD × 3 months on TKI | 27 (74) | 0 (HCQ)5 (HCQ+E) | 1.82 |
A = Afatinib; G = gefitinib; E= erlotinib; P = placebo; NR = Not Reported; EGFRm = EGFR mutant; PR = partial response; SD = stable disease; PD = progressive disease.
*
Response rate and PFS with MM-121 + E is in unselected patients.