Table 1.
Summary of clinical data of RET inhibitors for RET fusion-positive lung cancer.
| RET inhibitors | Multikinase inhibitors | Selective RET inhibitors | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cabozantinib | Vandetanib | Sorafenib | Lenvatinib | Sunitinib | Nintedanib | Ponatinib | Regorafenib | Pralsetinib | Selpercatinib | |||||
| Countries | USA | Global clinical trial (GLORY) | Japan | South Korea | Global clinical trial (GLORY) | Japan | Global clinical trial (GLORY) | Japan, USA, Singapore, Taiwan | Global clinical trial (GLORY) | Global clinical trial (GLORY) | Global clinical trial (GLORY) | Global clinical trial (GLORY) | Global clinical trial | Global clinical trial |
| Number of cases | 26 | 19 | 19 | 17 | 11 | 3 | 2 | 25 | 9 | 2 | 2 | 1 | Treated: 92 Treatment-naive: 29 |
Treated: 105 Treatment-naive: 39 |
| Methods of analysis | NGS, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | RT-PCR, FISH (both must be positive) | FISH, RT-PCR | NGS, RT-PCR, FISH (one must be positive) | RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | NGS | NGS, RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) | NGS, RT-PCR, FISH (one must be positive) |
| Fusion partners | KIF5B (16 cases), CCDC6 (1 case), TRIM33 (1 case), CLIP1 (1 case), ERC1 (1 case), other (6 cases) | NA | KIF5B (10 cases), CCDC6 (6 cases), other (3 cases) | KIF5B (5 cases), CCDC6 (2 cases), MYO5C (1 case), unknown (10 cases) | NA | KIF5B (1 case), CCDC6 (1 case), unknown (1 case) | NA | KIF5B (13 cases), CCDC6 (12 cases), unknown (1 case) | NA | NA | NA | NA | KIF5B (88 cases), CCDC6 (19 cases), other/unknown (14 cases) | KIF5B (59 cases), CCDC6 (24 cases), NCOA4 (2 cases), RELCH (2 cases), other/unknown (18 cases) |
| Response rate | 28% | 37% | 53% | 18% | 18% | 0% | 0% | 16% | 22% | 50% | 0% | 0% | Treated: 55% Untreated: 66% |
Treated: 64% Untreated: 85% |
| Progression-free survival (median) | 5.5 months | 3.6 months | 4.7 months | 4.5 months | 2.9 months | NA | NA | 7.3 months | 2.2 months | NA | NA | NA | Unreached | Treated: 17 months Untreated: Unreached |
| Overall survival (median) | 9.9 months | 4.9 months | 11.1 months | 11.6 months | 10.2 months | NA | NA | NA | 6.8 months | NA | NA | NA | Unreached | Unreached |
| Grade 3 and higher adverse events | 47% | NA | 58% | 28% | NA | 33% | NA | 92% | NA | NA | NA | NA | NA | 28% |
GLORY, Global Multicenter RET Registry; NGS, next-generation sequencing; FISH, fluorescence in situ hybridization; NA, not available.