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

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.

Informations de copyright

Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure AJR reports receiving consultation fees from EMD-Serono, Nanobiotix, Astellas, Novartis, Privo, and Galectin. WMS reports consultant (DSMB): Astra-Zeneca, Merck, Pfizer, Treadwell Therapeutics; consultant (other): Astra-Zeneca, Calico Life Sciences, Caremark/CVS, EMA Wellness, Fortress Biotech; speakers’ bureau: CME providers (sponsorship unknown): Applied Clinical Education, Dava Oncology, Global Academy for Medical Education, OncLive, PeerView, Research to Practice, Vindico; grant/research support (to institution): Abbvie, Amgen, Astra-Zeneca, Astellas (Medivation), Bayer, Bristol-Myers-Squibb, Bellicum, Boehringer-Ingelheim, Calithera, Clovis, Corvus, Eisai, Exilixis, Genentech (Roche), Johnson & Johnson (Janssen), Merck, Novartis, Pfizer, Seattle Genetics, X4Pharmaceuticals; stockholder: Fortress Biotech; expert witness: Apotex, DRL, Mylan, Sandoz; miscellaneous/editorial: Cancer (ACS), Up-To-Date, Kidney Cancer Journal. All other authors have declared no conflicts of interest.