A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t

Maria E. Cabanillas, Martin Schlumberger, Barbara Jarzab, Renato G. Martins, Furio Pacini, Bruce Robinson, Judith C. McCaffrey, Manisha H. Shah, Donald L. Bodenner, Duncan Topliss, Corina Andresen, James P. O'Brien, Min Ren, Yasuhiro Funahashi, Roger Allison, Rossella Elisei, Kate Newbold, Lisa F. Licitra, Steven I. Sherman, Douglas W Ball

Research output: Contribution to journalArticle

Abstract

American Cancer Society The results of this study demonstrate the psychometric validity of the Penn Arthralgia Aging Scale among breast cancer survivors on aromatase inhibitors. This scale captures women's perceptions of aging due to arthralgia and predicts incremental variance in depression, anxiety, and pain interference above and beyond joint pain severity

BACKGROUND 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). METHODS 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. RESULTS 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%). 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 a phase 3 trial. Cancer 2015;121:2749-2756.

Original languageEnglish (US)
Pages (from-to)2749-2756
Number of pages8
JournalCancer
Volume121
Issue number16
DOIs
StatePublished - Aug 1 2015

Fingerprint

Disease-Free Survival
Arthralgia
Confidence Intervals
Thyroid Neoplasms
Vascular Endothelial Growth Factor A
Disease Progression
Neoplasms
Receptor, Fibroblast Growth Factor, Type 1
Angiopoietin-2
Vascular Endothelial Growth Factor Receptor-1
Therapeutics
Platelet-Derived Growth Factor Receptors
Aromatase Inhibitors
Proto-Oncogenes
Angiogenesis Inducing Agents
Felidae
Oncogenes
Proteinuria
Psychometrics
Sarcoma

Keywords

  • biomarkers
  • differentiated thyroid cancer
  • lenvatinib
  • multikinase inhibitor
  • phase 2
  • radioiodine refractory

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Cabanillas, M. E., Schlumberger, M., Jarzab, B., Martins, R. G., Pacini, F., Robinson, B., ... Ball, D. W. (2015). A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t. Cancer, 121(16), 2749-2756. https://doi.org/10.1002/cncr.29395

A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t. / 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; O'Brien, James P.; Ren, Min; Funahashi, Yasuhiro; Allison, Roger; Elisei, Rossella; Newbold, Kate; Licitra, Lisa F.; Sherman, Steven I.; Ball, Douglas W.

In: Cancer, Vol. 121, No. 16, 01.08.2015, p. 2749-2756.

Research output: Contribution to journalArticle

Cabanillas, ME, Schlumberger, M, Jarzab, B, Martins, RG, Pacini, F, Robinson, B, McCaffrey, JC, Shah, MH, Bodenner, DL, Topliss, D, Andresen, C, O'Brien, JP, Ren, M, Funahashi, Y, Allison, R, Elisei, R, Newbold, K, Licitra, LF, Sherman, SI & Ball, DW 2015, 'A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t', Cancer, vol. 121, no. 16, pp. 2749-2756. https://doi.org/10.1002/cncr.29395
Cabanillas ME, Schlumberger M, Jarzab B, Martins RG, Pacini F, Robinson B et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t. Cancer. 2015 Aug 1;121(16):2749-2756. https://doi.org/10.1002/cncr.29395
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 ; O'Brien, James P. ; Ren, Min ; Funahashi, Yasuhiro ; Allison, Roger ; Elisei, Rossella ; Newbold, Kate ; Licitra, Lisa F. ; Sherman, Steven I. ; Ball, Douglas W. / A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t. In: Cancer. 2015 ; Vol. 121, No. 16. pp. 2749-2756.
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abstract = "American Cancer Society The results of this study demonstrate the psychometric validity of the Penn Arthralgia Aging Scale among breast cancer survivors on aromatase inhibitors. This scale captures women's perceptions of aging due to arthralgia and predicts incremental variance in depression, anxiety, and pain interference above and beyond joint pain severityBACKGROUND 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). METHODS 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. RESULTS 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{\%}). 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 a phase 3 trial. Cancer 2015;121:2749-2756.",
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author = "Cabanillas, {Maria E.} and Martin Schlumberger and Barbara Jarzab and Martins, {Renato G.} and Furio Pacini and Bruce Robinson and McCaffrey, {Judith C.} and Shah, {Manisha H.} and Bodenner, {Donald L.} and Duncan Topliss and Corina Andresen and O'Brien, {James P.} and Min Ren and Yasuhiro Funahashi and Roger Allison and Rossella Elisei and Kate Newbold and Licitra, {Lisa F.} and Sherman, {Steven I.} and Ball, {Douglas W}",
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T1 - A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated t

AU - Cabanillas, Maria E.

AU - Schlumberger, Martin

AU - Jarzab, Barbara

AU - Martins, Renato G.

AU - Pacini, Furio

AU - Robinson, Bruce

AU - McCaffrey, Judith C.

AU - Shah, Manisha H.

AU - Bodenner, Donald L.

AU - Topliss, Duncan

AU - Andresen, Corina

AU - O'Brien, James P.

AU - Ren, Min

AU - Funahashi, Yasuhiro

AU - Allison, Roger

AU - Elisei, Rossella

AU - Newbold, Kate

AU - Licitra, Lisa F.

AU - Sherman, Steven I.

AU - Ball, Douglas W

PY - 2015/8/1

Y1 - 2015/8/1

N2 - American Cancer Society The results of this study demonstrate the psychometric validity of the Penn Arthralgia Aging Scale among breast cancer survivors on aromatase inhibitors. This scale captures women's perceptions of aging due to arthralgia and predicts incremental variance in depression, anxiety, and pain interference above and beyond joint pain severityBACKGROUND 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). METHODS 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. RESULTS 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%). 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 a phase 3 trial. Cancer 2015;121:2749-2756.

AB - American Cancer Society The results of this study demonstrate the psychometric validity of the Penn Arthralgia Aging Scale among breast cancer survivors on aromatase inhibitors. This scale captures women's perceptions of aging due to arthralgia and predicts incremental variance in depression, anxiety, and pain interference above and beyond joint pain severityBACKGROUND 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). METHODS 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. RESULTS 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%). 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 a phase 3 trial. Cancer 2015;121:2749-2756.

KW - biomarkers

KW - differentiated thyroid cancer

KW - lenvatinib

KW - multikinase inhibitor

KW - phase 2

KW - radioiodine refractory

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