Multikinase Inhibitor Treatment Responses in Patients With RET-Rearranged NSCLC


Key Points

  • In patients with RET-rearranged NSCLC, response rates with the most commonly used multikinase inhibitors were 18% to 37%.
  • Median progression-free survival was 2.3 months.

In a report from the Global, Multicenter RET Registry in the Journal of Clinical Oncology, Gautschi et al documented response rates with multikinase RET inhibitors in patients with RET-rearranged non–small cell lung cancer (NSCLC).

Study Details

The study involved registry data (through April 2016) from 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States. Best response to RET tyrosine kinase inhibitor treatment outside a clinical trial was determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Patients had a median age of 61 years, 63% were never smokers, 98% had lung adenocarcinoma, and 91% had advanced disease. The most common RET rearrangement was KIF5B-RET, observed in 72% of cases.


A total of 53 tyrosine kinase inhibitor–naive patients received one or more RET tyrosine kinase inhibitors in sequence during the course of their treatment, including cabozantinib (Cometriq) in 21, vandetanib (Caprelsa) in 11, sunitinib (Sutent) in 10, sorafenib (Nexavar) in 2, alectinib (Alecensa) in 2, lenvatinib (Lenvima) in 2, nintedanib (Ofev) in 2, ponatinib (Iclusig) in 2, and regorafenib (Stivarga) in 1.

The best response to single-agent RET inhibition of any kind was complete response in 4% of patients, partial response in 22%, stable disease in 32%, progressive disease in 40%, and not evaluable in 2%. Response rates were 37% with cabozantinib, 18% with vandetanib, and 22% with sunitinib, with responses also being observed with lenvatinib and nintedanib. Median progression-free survival was 2.3 months, and median overall survival was 6.8 months.

The investigators concluded: “Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.”

Data management and statistical analysis for the study were supported by the University Hospital of Toulouse. The study was not funded by industry or any other third party.

Oliver Gautschi, MD, of Lucerne Cantonal Hospital in Switzerland, is the corresponding author of the Journal of Clinical Oncology article.

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