995PD - Phase II study of lenvatinib (LEN), a multi-targeted tyrosine kinase inhibitor, in patients (pts) with all histologic subtypes of advanced thyroid...
Date | 28 September 2014 |
Event | ESMO 2014 |
Session | Head and neck cancer |
Topics | Anticancer Agents Thyroid Cancer Translational Research Basic Principles in the Management and Treatment (of cancer) Therapy Biological Therapy |
Presenter | Shunji Takahashi |
Citation | Annals of Oncology (2014) 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340 |
Authors |
S. Takahashi1, M. Tahara2, N. Kiyota3, T. Yamazaki2, N. Chayahara4, K. Nakano1, R. Inagaki1, K. Toda5, T. Enokida2, H. Minami4, Y. Imamura4, T. Sasaki6, T. Suzuki6, K. Fujino7, C. Dutcus8
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Abstract
Aim
LEN is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRß, and showed a prominent improvement in progression free survival (PFS) in pts with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in Phase III study.
Methods
This is an open-label, multi-center phase II study conducted in Japan in pts with advanced thyroid cancer including RR-DTC, medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC). Institutional pathological diagnoses were accepted for eligibility. Pts were treated with a starting dose of LEN 24 mg once daily in 28 day cycles until disease progression or development of unmanageable toxicities. Primary objective was safety, and efficacy was assessed by RECIST 1.1 as secondary objective.
Results
From September 2012 to September 2013, 35 pts (all in PS 0-1, median age: 60.0, male/female: 13/22 ) were enrolled and evaluable for safety, including 22 pts with RR-DTC, 4 pts with MTC, and 9 pts with ATC. The most common adverse events (AEs; any Grade; Grade ≥3) included hypertension (86%; 43%), palmar-plantar erythrodysesthesia syndrome (74%; 6%), fatigue (71%; 3%), decreased appetite (69%; 9%), proteinuria (51%; 0%), stomatitis (51%; 0%), diarrhea (43%; 11%), nausea (40%; 6%) and dysphonia (31%; 0%). Almost all (34/35) subjects required dose reduction, however, no subjects required study drug withdrawal due to AEs. 34 pts were evaluable for efficacy, including 21 pts with RR-DTC, 4 pts with MTC, and 9 pts with ATC. The objective response rate (ORR) based on the investigator assessment was 47.6% in RR-DTC, 25.0% in MTC, and 33.3% in ATC, respectively. Median PFS was 6.5 mo (95% CI: 5.6 - 7.3) in MTC and 5.5 mo (95% CI: 1.4 -) in ATC, respectively. Median PFS has not been determined in RR-DTC.
Conclusions
AE profiles were generally similar to the data from previous clinical studies of lenvatinib with manageable toxicity with dose reduction and interruption. LEN demonstrated promising activity in all histologic subtypes of advanced thyroid cancer. Three of 9 pts with ATC have received administration of LEN for more than 6 month, which should be noteworthy.
Disclosure
S. Takahashi, M. Tahara and N. Kiyota: Advisory Board: Eisai. All other authors have declared no conflicts of interest.