Lenvatinib Plus Pembrolizumab for Patients With Radioiodine-Refractory Differentiated Thyroid Cancer
According to results from a multi-cohort study, lenvatinib plus pembrolizumab demonstrated efficacy and safety among patients with progressive, radioiodine (RAI)-refractory differentiated thyroid cancer.
As previously demonstrated, “lenvatinib, a potent multikinase inhibitor, improves progression-free survival (PFS) in patients with RAI-refractory differentiated thyroid cancer. However, most patients experience disease progression, warranting further therapy,” stated Jena French, PhD, University of Colorado Cancer Center, Aurora, Colorado, and coauthors. Here, “we evaluated the efficacy and safety of lenvatinib plus pembrolizumab in these patients.”
In this study, researchers enrolled 57 patients who were either naive to multikinase inhibitors (cohort 1; n = 30) or had experienced disease progression on lenvatinib (cohort 2; n = 27). Patients were assigned to receive daily lenvatinib (20 mg in cohort 1, dose at progression in cohort 2) plus 200 mg of pembrolizumab every 21 days. The primary end point was objective response rate (ORR). A key secondary end point was PFS.
At analysis, the confirmed ORR was 65.5% in cohort 1 and 16% in cohort 2. No complete responses were observed in cohort 1. Tumor histology, driver mutations, and immune-related biomarkers (PD-L1 expression, thyroid-specific antibody levels, and CD8*T-cell tumor infiltrate) did not correlate with response. Median PFS was 26.8 months with 12-month and 18-month PFS rates of 72% and 58%, respectively in cohort 1. Median PFS was 10 months in cohort 2. Incidence of increased baseline peripheral blood monocytes and neutrophil to lymphocyte ratio were associated with worse PFS in cohort 1. The adverse event profile was consistent with that observed in prior studies of patients treated with lenvatinib plus pembrolizumab.
“Lenvatinib plus pembrolizumab may enhance the durability of lenvatinib monotherapy in lenvatinib-naïve patients,” concluded Dr French et al. “The addition of pembrolizumab may be a viable salvage therapy for patients who have progressed on lenvatinib.”
Source:
French JD, Haugen BR, Worden FP, et al. Combination targeted therapy with pembrolizumab and lenvatinib in progressive, radioiodine-refractory differentiated thyroid cancers. Clin Cancer Res. Published online: September 3, 2024. doi: 10.1158/1078-0432.CCR-23-3417
