Lenvatinib as a Key First-Line Therapy in RAI-Refractory DTC

In an interview with Targeted Oncology^TM, Francis P. Worden, MD, professor of medicine at the University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, discusses his key takeaways for other oncologists treating patients with radioidine (RAI)-refractory differentiated thyroid cancer (DTC), including in those with BRAF-mutated, wild-type and BRAF untested tumors.

A US real-world experience study assessed the efficacy of lenvatinib (Lenvima) in a diverse cohort of patients with RAI-refractory DTC, encompassing those with BRAF-mutated, wild-type, and BRAF-untested tumors. The study, which examined patients initiating lenvatinib treatment between 2015 and 2020, analyzed response rates, progression-free survival, and overall survival.

The findings indicated that lenvatinib demonstrated consistent effectiveness regardless of the patients' BRAF mutation status. This suggests that lenvatinib could be a valuable first-line treatment option for a broader spectrum of patients with RAI-refractory DTC, highlighting its potential in BRAF-mutated disease as well.

Worden emphasizes the importance of next-generation sequencing after patients become refractory to iodine to identify potential new treatment targets. He notes the mutual exclusivity of common mutations in papillary thyroid cancer, with BRAF being the most prevalent, followed by less frequent RET and NTRK mutations.

Given the availability of highly effective targeted therapies for RET and NTRK alterations with manageable adverse event profiles, these should be prioritized upfront. For all other patients, including those with BRAF mutations, lenvatinib should be considered the first-line therapy upon disease progression or development of symptomatic disease.

He also suggests reserving BRAF and MEK inhibitor combinations as second-line treatment options in BRAF V600E-mutated patients after lenvatinib failure.

“In general, the message I would like to convey to those treating thyroid cancers is, we should be using lenvatinib as a frontline therapy and reserving targeted therapy for patients who are BRAF V600E-mutated as second-line therapy once the patients have failed upfront therapy with lenvatinib,” explains Worden.

REFERENCE:

Worden FP, Wirth LJ, Reynolds N, et al. Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutation status: A real-world view of effectiveness of lenvatinib monotherapy. J Clin Oncol. 2024;42(suppl 16):6098. doi.org:10.1200/JCO.2024.42.16_suppl.6098