Entry Detail
| General information | |
| Database: | DB00358 |
| Objective: | Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1FGFR4), plateletderived growth factor receptor ¦Á (PDGFR¦Á), ret protooncogene (RET), and vkit HardyZuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positivephase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodinerefractory, differentiated thyroid cancer (RRDTC). |
| Authors: | Cabanillas ME, et al |
| Title: | a phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodinerefractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. |
| Journal: | Cancer. |
| Year: | 2015 |
| PMID: | 25913680 |
| Trial Design | |
| Clinical Trial Id: | NCT00784303 |
| Agent: | lenvatinib |
| Target: | Alpha plateletderived growth factor receptor Mast/stem cell growth factor receptor Protooncogene tyrosineprotein kinase receptor ret VEGF receptor Fibroblast growth factor receptor |
| Cancer Type: | thyroid cancer |
| Cancer Subtype: | advanced, radioiodinerefractory, differentiated thyroid cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabel, singlearm, phase II trial |
| Key Patients Feature: | atients were aged 18 years who had histologically confirmed DTC (including papillary, follicular, H€ urthle cell, and poorly differentiated) that proved to be radioiodinerefractory (see online supporting information), evidenceof measurable and progressive disease (PD) (according tomodified Response Evaluation Criteria In Solid Tumors, version 1.0)21 within the previous 12 months, and anEastern Cooperative Oncology Group performance statusof 0 to 2. The receipt of prior chemotherapy or antiangiogenic therapy was permitted; however, it must have beendiscontinued at least 30 days before study entry |
| Biomarker: | Serum levels of 51 circulating cytokines and angiogenic factors |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received lenvatinib 24 mg once daily in 28day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFRtargeted therapy was permitted. |
| Primary End Point: | the objective response rate (ORR). |
| Secondary End Point: | progression free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors also were assessed. |
| Patients Number: | 58 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | After more than and equal to 14 months of followup, patients had an ORR of 50% (95% confidence interval [CI], 37%63%) with only partial responses reported. The median time to response was 3.6 months, the median response duration was 12.7 months, and the median PFS was 12.6 months (95% CI, 9.916.1 months). The ORR for patients who had received previous VEGF therapy (n = 17) was 59% (95% CI, 33%82%). Lower baseline levels of angiopoietin2 were suggestive of tumor response and longer PFS. Grade 3 and 4 treatmentemergent adverse events, regardless of their relation to treatment, occurred in 72% of patients and most frequently included weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). |
| Disease Control Rate: | 0.93 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12.6 months (95% CI, 9.916.1 months). |
| Median OS A vs. C: | NR(not reached) |
| Adverse Event(agent arm): | Grade 3 and 4 treatmentemergent adverse events, regardless of their relation to treatment, occurred in 72% of patients and most frequently included weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). |
| Conclusions: | In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in aphase 3 trial. Cancer 2015;12127492756. ? 2015 American Cancer Society. |