First-line lenvatinib and sorafenib in RR-DTC from a shared real-life context.

The kinase inhibitors lenvatinib and sorafenib represent the first-line options for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Comparative studies in the same study population or between similar cohorts are scarce. Our objective was to compare lenvatinib and sorafenib in naïve RR-DTC in a homogeneous real-life context. We performed a retrospective study involving two institutions from the Italian region Campania. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR), disease-control rate, adverse events graded ≥3, toxicity-related treatment withdrawal, and dose reductions/interruptions. Forty-eight RR-DTC patients were included (median follow-up 45.5 months): 24 received lenvatinib from 2015 to 2021 and 24 sorafenib from 2012 to 2016. The sorafenib group showed a higher disease-related symptoms rate (P = 0.022), tumor burden (P = 0.002), and cumulative radioiodine dose compared to lenvatinib. At univariate analysis, median PFS and OS were significantly longer for lenvatinib (30 and 53 months, respectively) compared to sorafenib (10 and 38 months, respectively) (P < 0.001 and = 0.037, respectively). At multivariate analysis, the significance was retained for PFS and lost for OS. ORR was higher for lenvatinib compared to sorafenib (P < 0.001). Dose reductions and interruptions were more frequent for lenvatinib compared to sorafenib (P = 0.003 and 0.01, respectively). In our real-life context, RR-DTC treated with first-line sorafenib had more advanced disease compared to lenvatinib. Lenvatinib exerted stronger antitumor activity (improved PFS and ORR) compared to sorafenib but did not improve OS. Sorafenib was more manageable.