During the development of Crizotinib, hundreds of gene mutations or rearrangements were screened, and RET was one of them. Recently, Kengo Takeuchi et al. published an article in Nature Medicine, stating that 44 ALK rearrangements, 13 ROS1 rearrangements, and 14 RET rearrangements were detected in 1529 lung cancer specimens, and Doron Lipson et al. examined 561 lung adenocarcinoma specimens and found 11 cases (2.0%) of KIF5B- RET gene rearrangement. No clinical studies have yet demonstrated whether Crizotinib is equally therapeutically sensitive in patients with RET rearrangements, and more and more in-depth studies are expected as a new molecular event. Vandetanib (ZD6474) is an inhibitor of the VEGFR, EGFR, and RET signaling pathways.Jin Soo Lee et al. designed the ZEPHYR study (Study 44) in which eligible patients were randomized in a 2:1 ratio to the vandetanib group (300 mg/d) and the placebo group until disease progression or an intolerable toxic reactions. The primary study metric was overall survival. The results showed that 924 patients were finally enrolled in the study, 617 in the vandetanib group and 307 in the placebo group. The median overall survival was 8.5 months and 7.8 months, respectively, and the overall survival rate in the vandetanib group was not better than that in the placebo group (hazard ratio=0.95, 95.2% CI:0.81-1.11, p=0.527). Progression-free survival (hazard ratio=0.63, p<0.001) and objective remission rates (2.6% and 0.7%; p= 0.028) were better in the vandetanib group than in the placebo group. The incidence of adverse events with vandetanib 300 mg was generally consistent with those reported in previous non-small cell lung cancer studies; more common adverse events were seen in the vandetanib group than in the placebo group, including diarrhea (46% vs. 11%), rash (42% vs. 11%), and hypertension (26% vs. 3%).