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Title: An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer
Authors: Bible, Keith C
Menefee, Michael E
Lin, Chia-Chi Josh
Millward, Michael J
Maples, William J
Goh, Boon Cher 
Karlin, Nina J
Kane, Madeleine A
Adkins, Douglas R
Molina, Julian R
Donehower, Ross C
Lim, Wan-Teck 
Flynn, Patrick J
Richardson, Ronald L
Traynor, Anne M
Rubin, Joseph
LoRusso, Patricia M
Smallridge, Robert C
Burton, Jill K
Suman, Vera J
Kumar, Aditi
Voss, Jessie S
Rumilla, Kandalaria M
Kipp, Benjamin R
Chintakuntlawar, Ashish
Harris, Pamela
Erlichman, Charles
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
radioactive iodine refractory
differentiated thyroid cancer
kinase inhibitor
Issue Date: 1-Sep-2020
Citation: Bible, Keith C, Menefee, Michael E, Lin, Chia-Chi Josh, Millward, Michael J, Maples, William J, Goh, Boon Cher, Karlin, Nina J, Kane, Madeleine A, Adkins, Douglas R, Molina, Julian R, Donehower, Ross C, Lim, Wan-Teck, Flynn, Patrick J, Richardson, Ronald L, Traynor, Anne M, Rubin, Joseph, LoRusso, Patricia M, Smallridge, Robert C, Burton, Jill K, Suman, Vera J, Kumar, Aditi, Voss, Jessie S, Rumilla, Kandalaria M, Kipp, Benjamin R, Chintakuntlawar, Ashish, Harris, Pamela, Erlichman, Charles (2020-09-01). An International Phase 2 Study of Pazopanib in Progressive and Metastatic Thyroglobulin Antibody Negative Radioactive Iodine Refractory Differentiated Thyroid Cancer. THYROID 30 (9) : 1254-1262. ScholarBank@NUS Repository.
Abstract: Introduction: Multikinase inhibitors have clinical activity in radioactive iodine refractory (RAIR) differentiated thyroid cancers (DTCs) but are not curative; optimal management and salvage therapies remain unclear. This study assessed clinical effects of pazopanib therapy in RAIR-DTC patients with progressive disease, examining in parallel biomarker that might forecast/precede therapeutic response. Methods: Assessment of responses and toxicities and of any association between thyroglobulin (Tg) changes cycle 1 and RECIST (response evaluation criteria in solid tumors) response to pazopanib therapy were prospectively undertaken in Tg antibody negative RAIR-DTC patients. RECIST progressive metastatic disease <6 months preceding enrollment was required. With a sample size of 68 (assuming 23 attaining partial response [PR]), there would be 90% chance of detecting a difference of >30% when the proportion of patients attaining PR whose Tg values decrease by >50% is >50% cycle 1 (one-sided α = 0.10, two sample test of proportions). Mean corpuscular volume (MCV) change or mutational status or pretreatment were also explored as early correlates of eventual RECIST response. Results: From 2009 to 2011, 60 individuals were treated and evaluated; (one additional patient withdrew; another was found ineligible before therapy initiation); 91.7% had previous systemic therapy beyond RAI. Adverse events included one death (thromboembolic) deemed possibly pazopanib associated. Twenty-two confirmed RECIST PRs resulted (36.7%, confidence interval; CI [24.6-50.1]); mean administered 4-week cycles was 10. Among 44 fully accessible patients, the Tg nadir was greater among the 20 attaining PR (median: -86.8%; interquartile range [IQR]: -90.7% to -70.9%) compared with the 28 who did not (median: -69.0%; IQR: -78.1% to -27.7%, Wilcoxon rank-sum test: p = 0.002). However, the difference in the proportion of PRs among those whose Tg fell ≥50% after cycle 1 versus those that did not were not significantly correlated (-23.5% [CI: -55.3 to 8.3]; Fisher's exact test p-value = 0.27). RECIST response was also not correlated with/predicted by early MCV change, receipt of prior therapy, or tumor mutational status. Conclusions: This trial prospectively confirmed pazopanib to have clinical activity and manageable toxicities in patients with progressive RAIR-DTC. Response to pazopanib, however, was not robustly forecast by early associated changes in Tg or MCV, by prior therapy, or by tumor mutational status. NCT00625846.
Source Title: THYROID
ISSN: 1050-7256
DOI: 10.1089/thy.2019.0269
Appears in Collections:Staff Publications

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