A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer

A J Rosenberg; C-Y Liao; T Karrison; J A de Souza; F P Worden; B Libao; M K Krzyzanowska; D N Hayes; E Winquist; V Saloura; K Prescott; V M Villaflor; T Y Seiwert; R B Schechter; W M Stadler; E E W Cohen; E E Vokes

doi:10.1016/j.annonc.2023.05.002

A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer

Ann Oncol. 2023 Aug;34(8):714-722. doi: 10.1016/j.annonc.2023.05.002. Epub 2023 May 13.

Authors

A J Rosenberg¹, C-Y Liao², T Karrison³, J A de Souza⁴, F P Worden⁵, B Libao⁶, M K Krzyzanowska⁷, D N Hayes⁸, E Winquist⁹, V Saloura¹⁰, K Prescott¹¹, V M Villaflor¹², T Y Seiwert¹³, R B Schechter⁶, W M Stadler², E E W Cohen¹⁴, E E Vokes²

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, USA; University of Chicago Comprehensive Cancer Center, Chicago, USA. Electronic address: Arirosenberg@medicine.bsd.uchicago.edu.
² Department of Medicine, University of Chicago, Chicago, USA; University of Chicago Comprehensive Cancer Center, Chicago, USA.
³ Department of Public Health Sciences, University of Chicago, Chicago, USA.
⁴ HCA Healthcare, Nashville, USA.
⁵ University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
⁶ Department of Medicine, University of Chicago, Chicago, USA.
⁷ Princess Margaret Cancer Centre, Toronto, Canada.
⁸ Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, USA.
⁹ Department of Oncology, University of Western Ontario and London Health Sciences Centre, London, Canada.
¹⁰ National Cancer Institute, Bethesda, USA.
¹¹ University of Illinois Chicago, Chicago, USA.
¹² City of Hope Comprehensive Cancer Center, Duarte, USA.
¹³ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, USA.
¹⁴ Moores Cancer Center at UC San Diego, La Jolla, USA.

PMID: 37182801
PMCID: PMC10696593 (available on 2024-08-01)
DOI: 10.1016/j.annonc.2023.05.002

Abstract

Background: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC.

Patients and methods: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible.

Results: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm.

Conclusions: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Keywords: antiangiogenic; cediranib; immunomodulation; lenalidomide; thyroid cancer; tyrosine kinase inhibitor.

Publication types

Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Humans
Infant
Iodine Radioisotopes / adverse effects
Lenalidomide / adverse effects
Receptors, Vascular Endothelial Growth Factor
Thyroid Neoplasms* / pathology
Vascular Endothelial Growth Factor A

Substances

Iodine-131
Iodine Radioisotopes
Lenalidomide
cediranib
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor

Grants and funding

UM1 CA186705/CA/NCI NIH HHS/United States