Table 1 Overview of novel agents regarding TKI in advanced NSCLC including systemic and intracranial efficacy
Identifier | Trials | Agents | Phase | Indication | Population | ORR* | mPFS | mOS | iRR | imPFS/iDOR | Toxcicty (≧ grade3) |
|---|---|---|---|---|---|---|---|---|---|---|---|
EGFR | |||||||||||
 NCT00818441 | ARCHER1070 | Dacomitinib | II | First-line | Advanced lung cancer with clinical (never-smoker or former light smokers) or molecular selected | 75.6% | 18.2 months | 40.2 months | NA | NA | NA |
 NCT01774721 | ARCHER1050 | Dacomitinib | III | First-line | Advanced NSCLC with one EGFR mutation (19Del or L858R) | 75.0% | 14.7 months | 34.1 months | NA | NA | 51% |
 NCT01802632 | AURA2 | Osimertinib | I/II | ≧ Second-line | Advanced NSCLC progressed after at least one prior treatment involving EGFR-TKI | 62.0% | 12.3 months | NR | 64.0% | 7.1 months | NA |
 NCT02151981 | AURA3 | Osimertinib | III | Second-line | Advanced NSCLC presented with EGFR sensitive mutations and T790m after first-line EGFR-TKI | 71.0% | 10.1 months | NR | 70.0% | 8.9 months | NA |
 NCT02296125 | FLAURA | Osimertinib | III | First-line | Untreated advanced NSCLC harbored sensitive EGFR mutations | 80.0% | 18.9 months | NR | 76.0% | 15.2 months | 22% |
 NCT02228369 | BLOOM | AZD3759 | I | ≧ Second-line | Advanced EGFR-mutant NSCLC with brain/leptomeningeal metastases progressed after EGFR-TKI and chemotherapy | 65.0% | NR | NA | 83.0% | NR | 17% (200 mg), 40% (300 mg) |
 NCT03066206 | / | Poziotinib | II | Unlimited | Advanced NSCLC bearing mutations/insertions of EGFR or HER2 exon 20 regardless of prior treatment | 43.0% | 5.6 months | NA | NA | NA | 60% |
ALK | |||||||||||
 NCT01283516 | ASCEND-1 | Ceritinib | I | Unlimited | Locally advanced or metastatic cancer harboring genetic alterations in ALK (NSCLC) | 72.0% (TN) 56.0% (PT) | 18.4 months (TN) 6.9 months (PT) | NA | 79.0% (TN)# 65.0% (PT)# | 8.2 months (TN) 11.1 months (PT) | 81% |
 NCT01685060 | ASCEND-2 | Ceritinib | II | > Second-line | Advanced ALK-rearranged NSCLC with asymptomatic or neurologically stable baseline brain metastasis | 38.6% | 5.7 months | NA | 45.0% | NA | 71.4% |
 NCT01828099 | ASCEND-4 | Ceritinib | III | First-line | Untreated metastatic non-squamous NSCLC harboring ALK rearrangement | 72.5% | 16.6 months | NR | 72.7% | 16.6 months | 78.0% |
 NCT01828112 | ASCEND-5 | Ceritinib | III | ≧ Second-line | Advanced ALK-positive NSCLC with at least two prior systemic treatment including crizotinib | 38.1% | 5.4 months | 18.1 months | 35.0% | 6.9 months | NA |
 NCT01801111 | / | Alectinib | II | Second-line | Advanced NSCLC with ALK rearrangement after disease progression of prior crizotinib | 50.0% | 8.9 months | NR | 57.0% | 10.3 months | NA |
 JapicCTI-132316 | J-ALEX | Alectinib (300 mg) | III | First-line | Advanced ALK-positive NSCLC with either chemotherapy naive or one previous chemotherapy | 92.0% | 25.9 months | NR | NA | NA | 32% |
 NCT0207584 | ALEX | Alectinib (600 mg) | III | First-line | Untreated advanced NSCLC harbored ALK rearrangment | 82.9% | 34.8 months | NR | 81.0% | 17.3 months | 41% |
 NCT03052608 | / | Loraltinib | I | Unlimited | Advanced NSCLC harbored ALK/ROS1 rearrangement regardless of prior treatments | 46.0% | 9.6 months | NA | 42.0% | NA | NA |
 NCT01970865 | / | Loraltinib | II | First-line | Untreated advanced NSCLC bearing ALK/ROS1-positive | 90.0% | NR | NR | 66.7% | NR | NA |
Second-line | Advanced ALK/ROS1 positive NSCLC with previous crizotinib | 69.5% | NR | NR | 87.0% | NR | NA | ||||
 NCT01449461 | / | Brigatinib | I/II | First-line | Treatment naive advanced ALK/EGFR positive NSCLC | 100.0% | NR | NA | 53.0% | 15.6 months | 36% |
Second-line | Advanced ALK/EGFR positive NSCLC with refractory disease after crizotinib | 62.0% | 14.5 months | NA | NA | NA | |||||
 NCT02737501 | ATLA-L1 | Brigatinib | III | First-line | Advanced ALK-positive NSCLC without previous ALK TKI treatment | 71.0% | NR | NR | 78.0% | NR | 61% |
ROS1 | |||||||||||
 NCT00585195 | / | Crizotinib | I | Unlimited | Advanced NSCLC with a ROS1 rearrangement | 72.0% | 19.2 months | NR | NA | NA | NA |
 NCT01945021 | / | Crizotinib | II | Unlimited | Advanced NSCLC with a ROS1 rearrangement | 71.7% | 15.9 months | 32.5 months | 73.9% | NA | 25.2% |
 NCT00585195 | / | Ceritinib | II | ≧ Second-line | Advanced ROS1-positive NSCLC progressed after at least one prior systemic treatment | 62.0% | 9.3 months (CT) 19.3 months (CN) | 24.0 months | 25.0%# | NA | 37.0% |
 NCT03052608 | / | Lorlatinib | I | Unlimited | Advanced NSCLC harbored ALK/ROS1 rearrangement regardless of prior treatments | 50.0% | 7.0 months | NA | 60.0% | NA | NA |