Lenalidomide does not improve upon treatment with cediranib in patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), according to research published in Annals of Oncology.
Patients who received lenalidomide and cediranib had similar outcomes as patients who received cediranib alone, researchers found. They noted, however, that the efficacy of cediranib alone was similar to the efficacy seen with other VEGFR-targeted tyrosine kinase inhibitors (TKIs).
This phase 2 trial (ClinicalTrials.gov identifier: NCT01208051) included 108 patients with DTC who had evidence of disease progression within the prior year, had no more than 1 prior line of systemic therapy, and were refractory to surgery or radioactive iodine.
Patients were randomly assigned to receive cediranib monotherapy (n=39) or cediranib plus lenalidomide (n=71). The median age was 62 years in the monotherapy arm and 64 years in the combination arm. Most patients were men (62% and 58%, respectively), and most had not received prior VEGF-targeted therapy (77% for both).
Patients were treated until disease progression, unacceptable toxicity, or patient or physician-initiated discontinuation.
At a median follow-up of 11 months, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the monotherapy and combination arms.
The median PFS was 14.8 months with cediranib alone and 11.3 months with cediranib plus lenalidomide (P =.36). At 2 years, the OS rate was 64.8% with cediranib and 75.3% with the combination (P =.80).
The objective response rate was also similar between the arms, at 44% with cediranib alone and 43% with the combination (P =.99). All responses were partial except for 1 complete response in the combination arm.
The most common grade 3-4 adverse events (AEs) that were at least possibly related to treatment were fatigue (26% in both arms), hypertension (26% in the monotherapy arm and 28% in the combination arm), and diarrhea (15% and 12%, respectively).
Treatment-related grade 3 or higher AEs that were more common in the combination arm than in the monotherapy arm were proteinuria (8.7% vs 5.1%), generalized muscle weakness (5.8% vs 0%), neutropenia (16% vs 2.6%), thrombocytopenia (4.3% vs 0%), and lymphopenia (4.3% vs 0%).
“Antiangiogenic TKIs are reaffirmed as the standard of care treatment approach in RAI-refractory DTC, while the addition of immunomodulatory agents does not improve progression-free survival, demonstrating alternative combinatorial approaches warrant evaluation in large multicenter studies,” the researchers wrote.
Disclosures: This research was partly supported by AstraZeneca and Celgene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rosenberg AJ, Liao C-Y, Karrison T, et al. A multicenter open-label randomized phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer. Ann Oncol. Published online May 12, 2023. doi:10.1016/j.annonc.2023.05.002