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A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine‐refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment
| Content Provider | Scilit |
|---|---|
| Author | O'Brien, James P. Cabanillas, Maria E. Schlumberger, Martin Jarzab, Barbara Martins, Renato G. Pacini, Furio Robinson, Bruce McCaffrey, Judith C. Shah, Manisha H. Bodenner, Donald L. Topliss, Duncan Andresen, Corina Ren, Min Funahashi, Yasuhiro Allison, Roger Elisei, Rossella Newbold, Kate Licitra, Lisa F. Sherman, Steven I. Ball, Douglas W. |
| Copyright Year | 2015 |
| Description | Journal: Cancer Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1‐VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1‐FGFR4), platelet‐derived growth factor receptor α (PDGFRα), ret proto‐oncogene (RET), and v‐kit Hardy‐Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine‐refractory, differentiated thyroid cancer (RR‐DTC). Fifty‐eight patients with RR‐DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28‐day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFR‐targeted therapy was permitted. The primary endpoint was the objective response rate (ORR) based on independent imaging review. Secondary endpoints included progression‐free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors also were assessed. After ≥14 months of follow‐up, 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, 9.9‐16.1 months). The ORR for patients who had received previous VEGF therapy (n = 17) was 59% (95% CI, 33%‐82%). Lower baseline levels of angiopoietin‐2 were suggestive of tumor response and longer PFS. Grade 3 and 4 treatment‐emergent 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%). 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 a phase 3 trial. Cancer 2015;121:2749‐2756. © 2015 American Cancer Society |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803478/pdf |
| Ending Page | 2756 |
| Page Count | 8 |
| Starting Page | 2749 |
| e-ISSN | 10970142 |
| DOI | 10.1002/cncr.29395 |
| Journal | Cancer |
| Issue Number | 16 |
| Volume Number | 121 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2015-04-24 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Endocrinology and Metabolism Differentiated Thyroid Cancer Multikinase Inhibitor Radioiodine Refractory Phase 2 |
| Content Type | Text |
| Resource Type | Article |
