Selpercatinib, a kinase inhibitor developed by Eli Lilly & Co., has shown promising results in the treatment of RET-mutant medullary thyroid cancer. According to the findings of a randomized phase 3 study presented at the ESMO Congress, selpercatinib outperformed its competitors, cabozantinib and vandetanib, in terms of improved outcomes and longer progression-free survival (PFS).
The study involved 291 patients who had experienced disease progression within the previous 14 months. They were randomly assigned to receive either selpercatinib or one of the approved agents, cabozantinib or vandetanib. Patients taking cabozantinib or vandetanib who experienced disease progression were able to switch to selpercatinib.
After a median follow-up period of 12 months, the results revealed that patients in the selpercatinib group had a significantly longer median PFS compared to those in the other group (not reached vs. 16.8 months). Furthermore, a higher percentage of patients on selpercatinib remained progression-free at 12 months (86.8% vs. 65.7%). Other efficacy outcomes, such as treatment failure-free survival and overall response rate, also favored selpercatinib over the competitors.
Dr. Julien Hadoux, a medical oncologist at Gustave Roussy in France, noted that these study results support selpercatinib as the first-line standard of care for patients with advanced RET-mutant medullary thyroid cancer. The findings also underscore the importance of RET selectivity and timely biomarker testing for patients with metastatic medullary thyroid cancer.
RET mutations occur in approximately 60% of sporadic medullary thyroid cancers and over 90% of hereditary cases. Selpercatinib received FDA approval last year for the treatment of adults with locally advanced or metastatic RET fusion-positive non-small cell lung cancer.
The LIBRETTO-531 trial aimed to determine the optimal first-line regimen for patients with RET-mutant medullary thyroid cancer. The results clearly demonstrate the superior efficacy of selpercatinib compared to cabozantinib and vandetanib. While overall survival data remain immature, the interim analysis showed promising results in favor of selpercatinib.
Patients assigned to cabozantinib or vandetanib experienced a higher percentage of dose reductions (79.2% vs. 38.9%) and treatment discontinuations (26.8% vs. 4.7%) due to adverse events, highlighting the better tolerability of selpercatinib.
In conclusion, the phase 3 study provides strong evidence supporting selpercatinib as the preferred first-line treatment for patients with advanced RET-mutant medullary thyroid cancer. The agent’s selectivity and efficacy demonstrated in this trial suggest the need for timely biomarker testing to guide treatment decisions for patients with metastatic medullary thyroid cancer. The results pave the way for improved outcomes and offer new hope for individuals battling this type of thyroid cancer.
