First-Line Lenvatinib May Improve PFS in Thyroid Cancer

Patients with ¹³¹I-refractory differentiated thyroid cancer (RR-DTC) assigned to lenvatinib in the SELECT trial who had no prior history of treatment with a vascular endothelial growth factor (VEGF) had a numerically higher progression-free survival compared with patients assigned to lenvatinib with prior VEGF exposure.

These results indicated that “lenvatinib may provide better outcomes when used first-line,” according to a poster presentation (abstract 6013) by Kate Newbold, MD, of the Royal Marsden National Health Service Foundation Trust in London, and colleagues presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

According to the poster, one of the key targets for sorafenib, the first targeted agent approved for RR-DTC, and other tyrosine kinase inhibitors is the VEGF signaling network, “which has been implicated in stimulating tumor angiogenesis and correlated with increased metastatic potential and poor clinical outcomes in thyroid cancer.”

In this study, Newbold and colleagues conducted a prespecified analysis of patients enrolled in the SELECT trial and compared the efficacy and safety of lenvatinib, an inhibitor of VEGF receptors 1–3, with placebo in patients who had not received a prior VEGF-targeted therapy (lenvatinib, n = 195; placebo, n = 104) and in those patients who had (lenvatinib, n = 66; placebo, n = 27).

The results showed a comparable progression-free survival benefit among patients treated with lenvatinib regardless of VEGF treatment status (18.7 months for VEGF-naïve patients vs 15.1 months for VEGF-treated patients). According to the researchers, “both subgroups demonstrated a progression-free survival benefit consistent with the overall SELECT population.”

In addition, the rate of overall response was similar for patients who were VEGF-naïve (65.6%) and those who had prior VEGF therapy (62.1%), as was the time to first objective response (1.9 vs 2.0 months).

The most common adverse events with lenvatinib for both VEGF-naïve and VEGF-treated patients were hypertension, diarrhea, decreased appetite, decreased weight, and nausea.

The researchers noted that patients without prior VEGF treatment received more cycles of lenvatinib than those with prior VEGF treatment; however, the safety profiles were similar between the two subgroups.