Medüler Tiroit kanserinde Selpercatinib adlı molekül ile daha iyi sonuç elde etmek mümkün
Medüler Tiroit kanserinde Selpercatinib adlı molekül ile daha iyi sonuç elde etmek mümkün
Medüler tiroit kanserlerinde RET mutasyonu %70 oranında görülür. Medüler tiroit kanserinde kemoterapi genellikle işe yaramaz ve hastalık üzerinde etkisizdir.
Bu tür kanser türünde RET aktivitesini bloke eden vandetanib ve cabozantinib gibi selektif olmayan tirozin kinaz inhibitörleri kullanılıyordu.
Son Avrupa Onkoloji Kongresinde Selektif RET inhibitörü olan Selpercatinib hastalıksız süreninin vandetanib ve cabozantinib göre %80 oranında artırdığı, yanıt oranı %70 çıkararak, diğer molekülere göre 2 kat artırdığı saptandı.
Yan etki ve tolere edilme oranın iyi olduğu ve bu çalışmayla daha önce tedavi görmemiş RET pozitif Evre IV Tiroit Medüler Kanserde ilk basamak tedavi seçeneği Selpercatinib adlı molekül oldu
Kaynak
ESMO 2023
Background
Selpercatinib is a highly selective and potent RET inhibitor approved for treatment of advanced RET-mutant medullary thyroid carcinoma (MTC) but has not been directly compared with approved multikinase inhibitors (MKI).
Methods
LIBRETTO-531 (NCT04211337) is a randomized phase 3 study comparing first-line selpercatinib versus physician’s choice of cabozantinib or vandetanib. Eligible patients had kinase inhibitor-naïve progressive disease documented in the 14 months prior to enrollment. The pre-planned interim efficacy analysis occurred after 59 progression-free survival (PFS) events. The primary endpoint was blinded independent central review (BICR)-assessed PFS.
Results
In total, 291 patients were randomized. Baseline characteristics were well-balanced between study arms. At a median follow-up of 12 months, median PFS by BICR was not reached with selpercatinib remaining inestimable (95% CI: NE, NE) and was 16.8 months (95% CI: 12.2, 25.1) with control (HR: 0.280, 95% CI: 0.165, 0.475; P<.0001); by investigator assessment the HR was 0.187 (95% CI: 0.109, 0.321; P<.0001). BICR overall response rate (ORR) was 69.4% (95% CI: 62.4, 75.8) with selpercatinib compared to 38.8% (95% CI: 29.1, 49.2) with control (odds ratio 3.7, 95% CI, 2.2, 6.3; P<0.0001). At a median follow-up of 15 months, overall survival (OS) was better with selpercatinib (HR: 0.374, 95% CI: 0.147, 0.949). The most common treatment-emergent adverse events observed with selpercatinib were hypertension, dry mouth, and diarrhea; and with control, diarrhea, palmar-plantar erythrodysaesthesia syndrome, and hypertension. In total, 38.9% of patients treated with selpercatinib had a dose reduction (versus 77.3% in control) and 4.7% discontinued treatment due to an adverse event (versus 26.8% in control).
Conclusions
The study met the interim analysis criteria of efficacy. First-line selpercatinib delivered markedly prolonged PFS, improved ORR, and better OS compared with MKI. This study highlights the importance of selectivity in targeting RET-mutant MTC. Selpercatinib should be considered the preferred first-line standard of care for patients with advanced RET-mutant MTC.
Clinical trial identification
NCT04211337
