Dr Hadoux on the Efficacy of Selpercatinib in RET-Mutant Medullary Thyroid Cancer

Julien Hadoux, MD, PhD, medical oncologist, attending physician, Gustave Roussy, Villejuif, France, discusses the efficacy of selpercatinib (Retevmo) in advanced, kinase inhibitor-naïve, RET-mutant medullary thyroid cancer as seen in the phase 3 LIBRETTO-531 (NCT04211337) trial.

Although this selective and potent RET inhibitor has demonstrated high activity and is approved for the treatment of patients with RET-mutant medullary thyroid cancer, it has not been directly compared with that of other approved multikinase inhibitors. Accordingly, this randomized study directly aimed to determine the optimal first-line regimen for this treatment population by assessing the efficacy of selpercatinib vs physician's choice of cabozantinib (Cabometyx) or vandetanib (Caprelsa).

Patients had a documented history of progressive disease without prior exposure to kinase inhibitors within 14 months of enrollment onto the study. A total of 291 patients were included across 176 cancer centers and the primary end point of the study was progression-free survival (PFS) by blinded independent central review.

Findings from the pre-planned interim analysis, which was conducted after 59 PFS events occurred, demonstrated that the median PFS was not reached with selpercatinib (95% CI: non-evaluable [NE]-NE), Hadoux reports. Conversely, median PFS was 16.8 months (95% CI: 12.2-25.1) with the control after a median follow-up of 12 months. This difference was significant and favored the selpercatinib arm, with a hazard ratio (HR) of 0.280 (95% CI: 0.165-0.475; P < 0.0001), he adds.

The BICR-assessed overall response rate (ORR) was higher with selpercatinib at 69.4% (95% CI: 62.4%-75.8%) compared with 38.8% (95% CI: 29.1%-49.2%) in the control group (odds ratio, 3.7; 95% CI, 2.2-6.3; P < 0.0001), Hadouz continues. At a median follow-up of 15 months, selpercatinib produced a superior overall survival benefit vs the control, with an HR of 0.374 (95% CI: 0.147-0.949; P = 0.0312).

Overall, the study met the interim analysis criteria for efficacy (two-sided P value < 0.0033), and the results support the use of selpercatinib as the standard of care for this patient population in the first-line, he details. Selpercatinib's efficacy and durability of response also highlights the importance of selectively targeting of RET-mutant medullary thyroid cancer, Hadoux concludes.