Lenvatinib plus pembrolizumab for the treatment of patients with non-BRAF mutated anaplastic thyroid cancer: A single center, phase 2 clinical trial

BACKGROUND: Dabrafenib (BRAF inhibitor) plus trametinib (MEK inhibitor) is approved for BRAF V600E-mutated anaplastic thyroid cancer (ATC), but ∼60% of tumors do not harbor BRAF V600E, leaving these patients without effective treatment options. METHODS: This was a phase 2 study of patients with BRAF wild type ATCs treated with concurrent lenvatinib 20 mg po daily and pembrolizumab 400 mg IV Q6 weeks. Those at high risk of bleeding could start on a reduced dose of lenvatinib. The primary endpoint was median OS and secondary endpoints were response rate and PFS. With a historical median OS of 3 months with single agent lenvatinib, the trial aimed to improve OS by an additional 3 months. RESULTS: Twenty-five patients with a median age of 62 years were enrolled, of which 64% were men. All patients had distant metastases at study entry. With a median follow-up time of 18.5 months (range 12-47.1) for alive patients, the median OS and PFS were 13 (95% CI: 7.8-35.6; p < 0.01), and 5.4 months (95% CI: 3.8-11.0), respectively. Best overall response in target lesions was 36%, including 1 complete and 8 partial responses. CONCLUSION: Lenvatinib + pembrolizumab demonstrates clinically meaningful OS in patients with metastatic, non-BRAF mutated ATC, a population with historically poor outcomes, supporting its use as an active therapeutic option. NCT04171622.