The addition of lenalidomide to cediranib failed to improve progression-free survival outcomes in patients with iodine 131–refractory differentiated thyroid cancer.
CHICAGO-The addition of lenalidomide to cediranib failed to improve progression-free survival (PFS) outcomes in patients with iodine 131–refractory differentiated thyroid cancer (DTC), according to results of a new study (abstract 6013) presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting held June 3–7 in Chicago. Cediranib alone showed promising results.
“Single agent VEGFR inhibitors and lenalidomide have shown activity in advanced DTC, but combination therapy has not been evaluated,” wrote study authors led by Jonas A. de Souza, MD, of the University of Chicago Medical Center.
In the study, a total of 110 patients were randomized in a 1:2 ratio to either cediranib alone or cediranib plus lenalidomide; two patients withdrew consent, leaving 108 evaluable. The median follow-up time was 9.9 months. All patients had measurable and progressive disease within 12 months of enrollment.
The study protocol called for a futility analysis after half of the expected PFS events (40 of 80 expected) occurred; this milestone occurred after 39 patients were randomized to cediranib and 68 to the combination therapy. The trial was stopped at that point and all patients were switched to cediranib alone, as the analysis showed that PFS was actually worse in the combination group.
After a further 10 months of follow-up, the PFS remained better in the group randomized to receive only cediranib. In that group, the 1-year PFS rate was 58%, compared with 45% in the group also receiving lenalidomide. At 2 years, the rates were 28% and 14%, respectively.
At that second analysis, the 1-year overall survival (OS) rates were similar between the groups, at 82% with cediranib alone and 84% in the combination therapy group. At 2 years, the OS rates were 62% and 66%, respectively.
A safety analysis was done based on adverse events occurring prior to the discontinuation of lenalidomide. The most common grade 3 or higher adverse event in both groups was fatigue (26% with cediranib and 25% with combination), followed by hypertension (23% and 22%, respectively), diarrhea (15% and 10%, respectively), and others.
During a poster discussion session, discussant Ann W. Gramza, MD, of Georgetown University, said that the negative results show that “More isn’t always better. But it did show that cediranib alone has encouraging results.” She noted, though, that it is not at all clear if cediranib will be investigated in further trials in this or other malignancies.