A Phase 2 Trial of the Multi-targeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer (MTC)
Mené sur 59 patients atteints d'un carcinome médullaire avancé de la thyroïde, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du lenvatinib
Introduction: Positive results of phase 1 studies evaluating lenvatinib in solid tumors including thyroid cancer prompted a phase 2 trial in advanced medullary thyroid carcinoma (MTC). Methods: 59 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 antivascular endothelial growth factor/receptor (anti-VEGF/R) 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% to 49%); all partial responses. ORR was comparable between patients with (35%) or without (36%) prior anti-VEGFR therapy. DCR was 80% (95% CI: 67% to 89%); 44% had stable disease. Amongst responders, median 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 interleukin-8 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 disease-control rate, and a short time to response in patients with documented progressive MTC. Toxicities were managed with dose modifications and medications.