Dr Hadoux discusses the results of the phase 3 study, LIBRETTO-531, which he presented at ESMO 2023.

The study compared the effectiveness of selpercatinib, a selective and potent RET inhibitor, with two approved multikinase inhibitors (MKI) for the treatment of advanced RET-mutant medullary thyroid carcinoma (MTC). The study involved 291 patients with kinase inhibitor-naïve progressive disease documented within the 14 months before enrollment.

The primary endpoint of the study was the progression-free survival (PFS) as assessed by a blinded independent central review (BICR). At a median follow-up of 12 months, selpercatinib showed significantly better results with a median PFS that was not reached (inestimable) compared to 16.8 months for the control group. The overall response rate (ORR) by BICR was 69.4% for selpercatinib, significantly higher than the 38.8% for the control group.

Additionally, at a median follow-up of 15 months, selpercatinib demonstrated better overall survival (OS) compared to the control group. The most common treatment-emergent adverse events for selpercatinib were hypertension, dry mouth, and diarrhea, whereas the control group experienced diarrhea, palmar-plantar erythrodysaesthesia syndrome, and hypertension. Fewer patients treated with selpercatinib required dose reductions and fewer discontinued treatment due to adverse events compared to the control group.

He concludes by noting that this study met the interim analysis criteria for efficacy, highlighting the importance of selectivity in targeting RET-mutant MTC, adding that selpercatinib has the potential to be the preferred first-line standard of care for patients with advanced RET-mutant MTC.