Vandetanib is a multi-target inhibitor of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), RET, BRK, TIE2, and other A multi-targeted inhibitor of tyrosine kinases with both anti-angiogenic and anti-proliferative effects.
Vandetanib was originally approved by the Food and Drug Administration (FDA) in 2011 for the treatment of medullary thyroid cancer. It wasn’t until 2017 that vandetanib took another step on the road to fighting cancer – it was recommended by the National Comprehensive Cancer Network (NCCN) guidelines for recurrent and metastatic non-small-cell lung carcinoma (NSCLC).
Why was it included in the NCCN guidelines but rejected by the FDA?
Actually, to date, the FDA has not approved vandetanib for the treatment of relapsed and metastatic NSCLC with RET rearrangements, but the US NCCN guidelines have given a 2A recommendation.
The rationale for this recommendation from the NCCN guidelines is that it has multiple targets, so where is the evidence?
In a Korean study, patients with relapsed or metastatic NSCLC who had received at least two types of chemotherapy and had RET rearrangements and were treated with 300 mg/d of vandetanib had an overall survival of 11.6 months, progression-free survival of 4.5 months, and a disease control rate of 65%.
In a Japanese study, patients with RET rearranged NSCLC treated with vandetanib had a 90% disease control rate and a 47% objective response rate, with 7 patients (37%) having even a 50% reduction in tumor volume, a median progression-free survival of 4.7 months, and a median overall survival of 11.1 months.
Based on these two studies, the NCCN guidelines give recommendations like the one above.
Precision treatment of RET rearranged NSCLC with tepid results from multi-target study
In fact, when vandetanib was first introduced, there were many clinical trials exploring its efficacy alone or in combination with chemotherapy in NSCLC based on its multitargeted nature, but unfortunately, only one study yielded positive results – progression-free survival with vandetanib in combination with docetaxel in treatment-naïve NSCLC 0.8 months longer relative to docetaxel alone. Although it was a positive result, 0.8 months is not encouraging at just 24 days.
It is clear that it is impractical to use vandetanib in all patients with advanced NSCLC, but it is possible to try it in patients with RET rearrangements. Although RET rearrangements are not as common as EGFR mutations, there is hope that there is such a targeted agent that can control the disease and extend life.
Vandetanib may cause heart rhythm changes
Common drug-related adverse reactions to vandetanib include rash, diarrhea, hypertension, anemia, and vomiting, most of which can be improved with symptomatic management.
But it is worth noting that it may alter the heart rhythm, and arrhythmias and sudden death have even been reported after treatment with this drug, so it should be avoided in combination with other drugs that can alter the heart rhythm; in addition, vandetanib is contraindicated in patients with hypocalcemia, hypokalemia, and hypomagnesemia, and hypocalcemia, hypokalemia, and/or hypomagnesemia should be corrected before use and monitored regularly during use. Electrolytes.
Summary
Vandetanib has been on the market for many years but has not been widely used in patients with NSCLC, and additional clinical studies are still underway. It has shown effectiveness in patients with RET rearranged NSCLC, suggesting that it may only be indicated for specific populations.