Vandetanib demonstrated clinical antitumor activity with a manageable safety profile in patients with advanced RET-rearranged non-small cell lung cancer (NSCLC), a study published in The Lancet Respiratory Medicine has shown.1
RET rearrangements are rare oncogenic alterations that occur in about 1% to 2% of NSCLC. Vandetanib is a multikinase inhibitor that possesses RET kinase activity. Therefore, researchers sought to evaluate the activity and safety of vandetanib in patients with advanced RET-rearranged NSCLC.
For the multicenter, open-label, phase 2 LURET study (UMIN-CTR Identifier: UMIN000010095), investigators enrolled 19 patients with advanced RET-rearranged NSCLC after screening 1536 patients with EGFR mutation-negative NSCLC. Of those enrolled, 53% had the KIF5B-RET fusion subtype, 31% had the CCDC6-RET subtype, and 42% had received 3 or more prior chemotherapy regimens.
All participants received vandetanib orally daily until disease progression or unacceptable toxicity.
The study showed that 53% (95% CI, 28-77) of the 17 evaluable patients achieved an objective response. The overall response rate was 47% (95% CI, 24-71) in the intention-to-treat population.
Researchers also found that median progression-free survival was 4.7 months (95% CI, 2.8-8.5) with vandetanib monotherapy. Median overall survival was 11.1 months (95% CI, 9.4-not reached).
Vandetanib appeared to possess a higher degree of activity in patients with the CCDC6-RET fusion subtype compared with those who harbored KIF5B-RET.
The most frequently reported grade 3 to 4 adverse events were hypertension, diarrhea, rash, dry skin, and QT interval prolongation.
Given the efficacy of vandetanib in RET-rearranged NSCLC, the findings suggest that further large confirmatory trials are warranted to establish the role of vandetanib in this patient population.
1. Yoh K, Seto T, Satouchi M, et al. Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. Lancet Respir Med. 2016 Nov 4. doi: 10.1016/S2213-2600(16)30322-8. [Epub ahead of print]