In fact, if it is true that the main safety endpoints (G ≥3 AE, dose reduction, and drug discontinuation rates) have improved with the use of RET-Is compared to multi-TKis, there are some toxicities correlated to the inhibition of VEGFR-2 (hypertension primarily), and there others whose mechanisms are not well known (also attributable to the RET inhibition itself), with non-negligible rates of grade 3 or higher, such as the following: hypertension (both drugs), medullary toxicity (pralsetinib, thrombocytopenia, both drugs), pneumonitis (pralsetinib), and QTc prolongation (selpercatinib). This evidence concerns the gene KDR and hypertensive disorder.