A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer.
Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW, McCaffrey J, Newbold K, Allison R, Martins RG, Licitra LF, Shah MH, Bodenner D, Elisei R, Burmeister L, Funahashi Y, Ren M, O'Brien JP, Sherman SI
Clin Cancer Res 22 44-53 01/01/2016
PURPOSE: Positive results of phase I studies evaluating lenvatinib in solid tumors, including thyroid cancer, prompted a phase II trial in advanced medullary thyroid carcinoma (MTC).
EXPERIMENTAL DESIGN: Fifty-nine patients with unresectable progressive MTC per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 within the prior 12 months received lenvatinib (24-mg daily, 28-day cycles) until disease progression, unmanageable toxicity, withdrawal, or death. Prior anti-VEGFR therapy was permitted. The primary endpoint was objective response rate (ORR) by RECIST v1.0 and independent imaging review.
RESULTS: Lenvatinib ORR was 36% [95% confidence interval (CI), 24%-49%]; all partial responses. ORR was comparable between patients with (35%) or without (36%) prior anti-VEGFR therapy. Disease control rate (DCR) was 80% (95% CI, 67%-89%); 44% had stable disease. Among responders, median time to response (TTR) was 3.5 months (95% CI, 1.9-3.7). Median progression-free survival (PFS) was 9.0 months (95% CI, 7.0-not evaluable). Common toxicity criteria grade 3/4 treatment-emergent adverse events included diarrhea (14%), hypertension (7%), decreased appetite (7%), fatigue, dysphagia, and increased alanine aminotransferase levels (5% each). Ret proto-oncogene status did not correlate with outcomes. Low baseline levels of angiopoietin-2, hepatocyte growth factor, and IL8 were associated with tumor reduction and prolonged PFS. High baseline levels of VEGF, soluble VEGFR3, and platelet-derived growth factor BB, and low baseline levels of soluble Tie-2, were associated with tumor reduction.
CONCLUSIONS: Lenvatinib had a high ORR, high DCR, and a short TTR in patients with documented progressive MTC. Toxicities were managed with dose modifications and medications.