Real-world efficacy and safety of selpercatinib in RET-mutant medullary thyroid cancer at a Tertiary Referral Center.

[OBJECTIVE] Selective RET inhibition with selpercatinib significantly improved outcomes in advanced RET-mutant medullary thyroid cancer (MTC). However, data from endocrine oncology practice are limited, particularly in heterogeneous treatment-naive and pretreated patients. Evaluating real-world effectiveness and safety is essential to reaffirm clinical trial results.

[DESIGN] Retrospective, single-center study.

[METHODS] We analyzed patients with RET-mutant MTC treated with selpercatinib between March 2021 and May 2025 at the Essen Endocrine Tumor Center. Clinical characteristics, treatment outcomes as well as frequency and longitudinal course of adverse events (AEs) were assessed.

[RESULTS] Thirty-one patients with advanced RET-mutant MTC (87% with distant metastases; median age 54 years; 84% sporadic) were included. First-line selpercatinib (52%) treatment resulted in significantly longer median progression-free survival (PFS) (not reached vs. 18.3 months) and higher objective response rate (ORR) (81% vs. 33%) compared to later-line use. One-year PFS rate was 100% for first-line and 60% for further-line treatment. ORR was significantly higher in patients without bone metastases (90% vs 43%). Age at treatment initiation, sex, and RET mutation subtype did not impact ORR or PFS. The most common AEs included hypertension (58.6%) and erectile dysfunction (55.6%). Grade ≥3 events occurred in 37.5% of patients, with hypertension most frequent. Treatment interruptions and dose reductions were required in 22.6% of patients, primarily due to QTc prolongation and fatigue. Three patients (9.7%) discontinued treatment permanently due to AEs.

[CONCLUSIONS] In real-word settings, selpercatinib showed high efficacy and tolerability, particularly as first-line treatment. Our findings support its use as the preferred initial targeted treatment for RET-driven MTC beyond clinical trial populations.