The efficacy of selperkatinib in the first and subsequent lines of targeted therapy in unresectable progressive medullary thyroid cancer with a mutation in the gene RET

Introduction. RET gene mutations are frequently detected in patients with medullary thyroid cancer (MTC). In unresectable and metastatic disease, multikinase inhibitors are used, however, their efficacy is limited, and toxicity may require therapy adjustment. Selpercatinib is a selective RET inhibitor that has demonstrated high efficacy in RET-positive MTC.

Aim. To compare the efficacy and safety of selpercatinib when used in the first versus subsequent lines of targeted therapy in patients with progressive unresectable and / or metastatic RET-mutated MTC.

Materials and methods. The study included 20 patients with MTC divided into two groups. In Group А (n = 10), selpercatinib was used as first-line therapy, in Group Б – in the second or third line after vandetanib and / or cabozantinib. The median follow-up was 43.5 and 9.25 months, respectively. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours 1.1 and by analyzing serum calcitonin dynamics. Adverse events were also analyzed.

Results. In Group А, the mean duration of therapy was 42.9 months. Complete response was achieved in 4 (40 %) patients, stable disease⁠ – in 5 (50 %), and partial response – in 1 (10 %). Disease progression at 22 months from treatment initiation was noted in 1 case. All patients are alive and continue therapy. In 4 (40 %) patients, calcitonin levels decreased to reference values. In Group Б, the mean duration of therapy was 11.8 months. Partial response was registered in 4 (40 %) patients and stable disease in 6 (60 %); no complete responses were observed. One patient died due to disease progression. A decrease in calcitonin levels was observed, but normalization was not achieved. Arterial hypertension was the most common adverse event. Treatment was not discontinued in any patient due to toxicity.

Conclusion. Selpercatinib has demonstrated high efficacy and acceptable safety in RET-positive MTC. Its use in the first line was characterized by a higher complete response rate and a more pronounced decrease in calcitonin levels compared with subsequent lines. However, administration of the drug following progression on vandetanib and / or cabozantinib also allowed for disease control and represented a reasonable treatment option.