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.
A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t
ELISEI, ROSSELLA;
2015-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
