Table 1. Summary of ALK inhibitors studies in crizotinib-naïve and resistant advanced NSCLC patients.
| Drug | Study | Line | Phase | N | Crizotinib-naive | Crizotinib-resistant | Ref | |||
|---|---|---|---|---|---|---|---|---|---|---|
| ORR [n (%)] | mPFS (m) | ORR [n (%)] | mPFS (m) | |||||||
| Crizotinib | ||||||||||
| PROFILE 1001 | ≥1st line | I | 143 | 60.8 | 9.7 | – | – | (5) | ||
| PROFILE 1005 | ≥2nd line | II | 255 | 53 | 8.5 | – | – | (6) | ||
| PROFILE 1007 | ≥2nd line | III | 173 | 65 | 7.7 | – | – | (7) | ||
| PROFILE 1014 | 1st line | III | 172 | 74 | 10.2 | – | – | (8) | ||
| Alectinib (RO5424802) | ||||||||||
| AF-001JP* | ≥2nd line | I/II | 43 | 93.5 | NA | – | – | (2) | ||
| AF-002JG | ≥2nd line | I/II | 44 | – | – | 55 | NA | (3) | ||
| NP28761 | ≥2nd line | II | 69 | – | – | 48 | 8.1 | (4) | ||
| NP28673 | ≥2nd line | II | 122 | 50 | 8.9 | (9) | ||||
| J-ALEX* | 1st line | III | 103 | 91.6 | NR | – | – | (10) | ||
| Ceritinib (LDK378) | ||||||||||
| ASCEND-1 | ≥2rd line | I | 246 | 60/83 [72] | 18.4 | 92/163 [56.4] | 6.9 | (11) | ||
| ASCEND-2 | ≥2rd line | II | 140 | – | – | 38.6 | 5.7 | (12) | ||
| ASCEND-3 | ≥2rd line | II | 124 | 63.7 | 11.1 | – | – | (13) | ||
| Brigatinib (AP26113) | ||||||||||
| NCT01449461 | ≥2rd line | I/II | 65 | 7/7 [100] | 14 | 45/65 [69] | 11.8 | (14) | ||
| ALTA** | ≥2rd line | II | 222 | – | – | A: 51/112 [46] | 8.8 | (15) | ||
| B: 59/110 [54] | 11,1 | |||||||||
| Lorlatinib (PF-06463922) | ||||||||||
| NCT01970865 | ≥2rd line*** | I/II | 41 | – | – | 46% | 11.4 | (16) | ||
| Entrectinib (RXDX-101) | ||||||||||
| NTC02097810 | ≥2rd line+ | I/II | 7 | – | – | 57% | NA | (17) | ||
*, Japanese population; preliminary data; **, randomized trial of brigatinib Arm A: 90 mg, Arm B: 180 mg; ***, 3 cohorts, 1 (with ALK and ROS1 alterations) allowed inclusion with progression under previous 2 ALK inhibitors; +, cohort of ALK and ROS1 rearrangement, allowing the inclusion with progression under previous 2 ALK inhibitors; NA, not available; NR, not reached.