Lorlatinib in NSCLC patients with prior progression on targeted therapy.
| Study | N, comments | ECOG PS | Method of ALK testing | Prior ALK TKI treatment | Duration of response to the last TKI | ORR(%) | IC-ORR(%) | PFS (months) | OS (months), defined as the time from lorlatinib initiation to death | OS (months), defined as the time from the diagnosis of metastatic disease to death | Mode recruitment |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Present study | 82 | 0/1: 80.5%;2: 19.5% | PCR/NGS: 43.9%FISH: 45.1%IHC: 11.0% | 1 line: 75.6%2 lines: 19.5%3 lines: 4.9% | 4–12 months: 37.8%;≥ 12 months: 62.2% | 64.6 | 66.2 (43/65) | All: 66.71 prior TKI: 66.7≥ 2 prior TKIs: 75.0 | All: not reached1 prior TKI: Not reached≥ 2 prior TKIs: 65.7 | Not reached | Expanded access and routine clinical use |
| Solomon et al. [7], Ou et al. [11] | 198 | 0/1: 96.4%;2: 3.6% | FISH or IHC (% not reported) | 1 line: 44.0%2 lines: 32.8%3 lines: 21.2%≥ 4 lines: 2.0% | Not reported | 47.0 | 63.0 (51/81) | All: 7.3Previous crizotinib: not reachedPrevious non-crizotinib TKI: 5.5≥ 2 prior TKIs: 6.9 | All: not reachedPrevious crizotinib: not reachedPrevious non-crizotinib TKI: 37.4≥ 2 prior TKIs: 20.7 | Not reported | Clinical trial |
| Calles et al. [12] | 61, with at least one prior 2nd-gen TKI | 0/1: 72.1%;2/3: 13.1%;Unknown: 14.7% | FISH: 54.4%;IHC: 31.1%;PCR/NGS: 5.9% | 1 line: 5.3%2 lines: 36.8%3 lines: 19.3%≥ 4 lines: 35.1% | Not reported | 32.8 | 58.8 (10/17) | All: 11.21 prior TKI: 15.12 prior TKIs: 11.1≥ 3 prior TKIs: 7.6 | All: 13.51 prior TKI: 17.42 prior TKIs: 13.5≥ 3 prior TKIs: 12.0 | 45.8 | Expanded access |
| Tian et al. [13] | 57 | 0/1: 87.7%;2/3: 12.3% | IHC: 35.4%NGS: 40.0%FISH: 1.5%≥2 methods: 23.1% | 1 line: 38.5%≥ 2 lines: 49.2% | Not reported | 49.2 | 45.2 (19/42) | 1 prior TKI: 49.7≥ 2 prior TKIs: 12.2 | Not reached | Not reported | Not reported |
| Shih et al. [14] | 54, with at least one prior 2nd-gen TKI | 0/1: 36.8%;2: 9.5%;Unknown: 54.0% | Not reported | Patients with at least one 2nd-gen TKI1 line: 18.5%2 lines: 50.0%≥ 3 lines: 31.5% | Not reported | 13.7 | 30.6 (11/36) | All: 9.21 prior TKI: not reached2 prior TKIs: 6.1≥ 3 prior TKIs: 8.1 | All: not reached1 prior TKI: not reached2 prior TKIs: not reached≥ 3 prior TKIs: 21.2 | Not reported | Expanded access |
| Biswas et al. [15] | 38 | Not reported | FISH: 50.0%;IHC: 50.0% | Not reported | Not reported | 70.3 | Not reported | Not reached | Not reported | 93.1 | Expanded access |
| Goto et al. [16] | 51, with prior alectinib given the 1st line | 0/1: 58.9%;2–4: 17.6%;Unknown: 23.5% | Not reported | 1 line of alectinib: 70.6%1 line of alectinib followed by chemotherapy or another TKI: 29.4% | Not reported | 35.7 | 28.6 (6/21) | 11.1 | Not reported | Not reported | Not reported |
| Alexander et al. [17] | 38 | 0/1: 76.0%;≥ 2: 24.0%;Unknown: 34.2%; | IHC screened, then validated by FISH | 1 line of 2nd-gen: 42.1%;≥ 2 lines of 1st- and 2nd-gen: 42.1%;≥ 2 lines of 2nd-gen only: 15.8%; | Not reported | 44.4 | 35.3 (6/17) | All: 7.31 line of 2nd-gen: 10.5≥ 2 lines of 1st- and 2nd-gen: 34.6≥ 2 lines of 2nd-gen only: 1.1 | All: 19.91 line of 2nd-gen: 19.9≥ 2 lines of 1st and 2nd-gen: 34.6≥ 2 lines of 2nd-gen only: 2.1 | All: 45.01 line of 2nd-gen: 116.3≥ 2 lines of 1st and 2nd-gen: 39.4≥ 2 lines of 2nd-gen only: 32.0 | Expanded access |
| Baldacci et al. [18] | 208, mainly with prior crizotinib and 2nd-gen TKI | 0/1: 60.1%;≥ 2: 23.1%;Unknown: 16.8% | Not reported | 1 line: 9.6%2 lines: 57.7%≥ 3 lines: 32.7% | Not reported | 49.0 | 56.3 (90/160) | 9.9 | 32.9 | 97.3 | Expanded access |
| Hochmair et al. [19] | 37 | Not reported | IHC: 35.1%FISH: 45.9%NGS: 2.7%≥ 2 methods: 16.2% | 1 line: 27.0%2 lines: 35.1%3 lines: 35.1%4 lines: 2.7% | Not reported | 43.2 | 62.5 (5/8) | Not reported | All: 10.21 line of TKI: 6.42 lines of TKI: 31.2≥ 3 lines of TKI: 7.1 | Not reported | Expanded access |
| Frost et al. [20] | 52 | 0/1: 90.4%;2: 1.9%;Unknown: 7.7% | Not reported | Not reported | Not reported | 42.4 | Not reported | 7.0 | 24.7 | 79.6 | Expanded access |
| Zhu et al. [21] | 76 | Not reported | FISH: 46.1%IHC: 46.1%NGS: 9.2%PCR: 6.6%≥ 2 methods in 6 cases | 1 line: 13.2%;2 lines: 59.2%;≥ 3 lines: 27.6% | Not reported | 32.8 | 34.6 (18/52) | All: 9.31 line of TKI: 9.32 lines of TKI: not reached≥ 3 lines of TKI: 6.5 | Not reported | All: not reached5-year OS:1 line of TKI: 85.7%≥ 2 line of TKI: 77.9%≥ 3 line of TKI: 72.5% | Expanded access |
| Peled et al. [22] | 106 | 0/1: 61.3%;≥ 2: 14.2%;Unknown: 24.5% | FISH: 76.4%;IHC: 31.1%;NGS: 7.5%;PCR: 13.2%;≥ 2 methods in some cases | Not reported | Not reported | 59.7 | 61.5 (40/65) | Not reported | Not reported | 89.1 months | Expanded access |
ALK: anaplastic lymphoma kinase; ECOG PS: Eastern Cooperative Oncology Group Performance Status; FISH: fluorescence in situ hybridization; gen: generation; IC-ORR: intracranial objective response rate; IHC: immunohistochemistry; NGS: next-generation sequencing; NSCLC: non-small cell lung cancer; ORR: objective response rate; OS: overall survival; PCR: polymerase chain reaction; PFS: progression-free survival; TKI: tyrosine kinase inhibitor.