- Email: [email protected]
Phase Ii Study of Lenvatinib (Len), a Multi-Targeted Tyrosine Kinase Inhibitor, in Patients (Pts) with All Histologic Subtypes of Advanced Thyroid Cancer (Differentiated, Medullary and Anaplastic)
Annals of Oncology 25 (Supplement 4): iv340–iv356, 2014 doi:10.1093/annonc/mdu340.10
head and neck cancer 995PD
S. Takahashi1, M. Tahara2, N. Kiyota3, T. Yamazaki2, N. Chayahara3, K. Nakano1, R. Inagaki1, K. Toda4, T. Enokida2, H. Minami3, Y. Imamura3, T. Sasaki5, T. Suzuki5, K. Fujino6, C. Dutcus7 1 Medical Oncology, Japanese Foundation for Cancer Research, Tokyo, JAPAN 2 Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, JAPAN 3 Medical Oncology and Hematology, Kobe University Hospital, Kobe, JAPAN 4 Division of Head and Neck Surgery, Japanese Foundation for Cancer Research, Tokyo, JAPAN 5 Oncology Group, Clinical Development, Eisai Co., Ltd, Tokyo, JAPAN 6 Biostatistics, Biostatistics/clinical Analytics, Cclo, Eisai, Tokyo, JAPAN 7 Clinical Development, Eisai, Woodcliff lakes, NJ, USA
abstracts
Aim: LEN is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ, and showed a prominent improvement in progression free survival (PFS) in pts with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in Phase III study.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv343/2241706 by guest on 24 October 2019
PHASE II STUDY OF LENVATINIB (LEN), A MULTI-TARGETED TYROSINE KINASE INHIBITOR, IN PATIENTS (PTS) WITH ALL HISTOLOGIC SUBTYPES OF ADVANCED THYROID CANCER (DIFFERENTIATED, MEDULLARY AND ANAPLASTIC)
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.
head and neck cancer 995PD
S. Takahashi1, M. Tahara2, N. Kiyota3, T. Yamazaki2, N. Chayahara3, K. Nakano1, R. Inagaki1, K. Toda4, T. Enokida2, H. Minami3, Y. Imamura3, T. Sasaki5, T. Suzuki5, K. Fujino6, C. Dutcus7 1 Medical Oncology, Japanese Foundation for Cancer Research, Tokyo, JAPAN 2 Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, JAPAN 3 Medical Oncology and Hematology, Kobe University Hospital, Kobe, JAPAN 4 Division of Head and Neck Surgery, Japanese Foundation for Cancer Research, Tokyo, JAPAN 5 Oncology Group, Clinical Development, Eisai Co., Ltd, Tokyo, JAPAN 6 Biostatistics, Biostatistics/clinical Analytics, Cclo, Eisai, Tokyo, JAPAN 7 Clinical Development, Eisai, Woodcliff lakes, NJ, USA
abstracts
Aim: LEN is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ, and showed a prominent improvement in progression free survival (PFS) in pts with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in Phase III study.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv343/2241706 by guest on 24 October 2019
PHASE II STUDY OF LENVATINIB (LEN), A MULTI-TARGETED TYROSINE KINASE INHIBITOR, IN PATIENTS (PTS) WITH ALL HISTOLOGIC SUBTYPES OF ADVANCED THYROID CANCER (DIFFERENTIATED, MEDULLARY AND ANAPLASTIC)
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.