Table 2.
Safety and efficacy of nonspecific multikinase inhibitors (MKIs) in RET-aberrant malignanciesa
| Cabozantinib | Vandetanib | Lenvatinib | Others | |
|---|---|---|---|---|
| Efficacy and safety in patients with NSCLC | RET + NSCLC (MSKCC study) (n = 26) - ORR = 28%, mPFS = 5.5 months, OS = 9.9 months - ≥G3AEs = 69%, - 73% dose-reduced, - 8% discontinued |
RET + NSCLC (Japan LURET trial) (n = 19) - ORR = 47%, mPFS = 4.7 months, mOS = 11.1 months - 53% dose-reduced, - 21% discontinued RET + NSCLC (Korea trial) (n = 18) - ORR = 18%, - PFS = 4.5 months, - OS = 11.6 months - 27% dose-reduced |
RET + NSCLC (Phase II study) (n = 25) - ORR = 16%, - mPFS = 7.3 months - 64% dose-reduced, 20% discontinued |
GLORY RET registry Cabozantinib in RET + NSCLC (n = 19) - ORR = 37%, - mPFS = 3.6 months, - mOS = 4.9 months Vandetanib in RET + NSCLC (n = 11) - ORR = 18%, - mPFS = 2.9 months, - mOS = 10.2 months Sunitinib in RET + NSCLC (n = 9) - ORR = 22%, - mPFS = 2.2 months - mOS = 6.8 months |
| Efficacy and safety in patients with thyroid cancers | MTC (EXAM trial) - ORR = 32%, - PFS = 14 months, - OS = 44.3 months - ≥G3AEs = 69%, 79% dose-reduced, - 16% discontinued |
MTC (ZETA trial) - ORR = 45%, - PFS 30.5 months, - OS NA - ≥G3AEs = 69%, 35% dose-reduced, - 12% discontinued |
MTC (Phase II study) (n = 59) - ORR = 36%, - mPFS = 9.0 months, - mOS = 16.6 months - 59% dose-reduced, 24% discontinued |
|
| FDA approval timeline | Cabozantinib in metastatic MTC (November 2012) | Vandetanib in metastatic MTC (April 2011) | Lenvatinib in progressive, RAI-refractory DTC (February 2015) | Sorafenib in progressive, RAI-refractory DTC (November 2013) |
a
Abbreviations: ≥G3AEs, grade 3 and above adverse events; mOS, median overall survival; mPFS, median progression-free survival; MSKCC, Memorial Sloan-Kettering Cancer Center; NA, not available; NSCLC, non-small cell lung cancer; ORR, objective response rate; RAI, radioactive iodine.