Tyrosine Kinase Inhibitor Therapy in Metastatic Medullary Thyroid Carcinoma: Real-World Data from Turkish Oncology Group
Makaleler > Tam Makale · 2026
Yazarlar: Sedat Yıldız, Hacer Demir, Talha Özüdoğru, Damla Günenç, Zeynep Sıla Gökdere, Hayati Arvas, Zuhat Urakçı, Seda Jeral Evinç, Özkan Alan, Rumeysa Çolak, Mesut Yılmaz, Esra Aşık, Atila Yıldırım, Ali Kaan Güren, Osman Köstek, Berkan Karabuğa, Öztürk Ateş, Canberk Şencan, Tuğba Yavuzşen, Şuheda Ataş İpek, İsmail Oğuz Kara, Teoman Şakalar, Ahmet Cebeli Gökay, Havva Yeşil Çınkır, Ahmet Kürşad Dişli, Mevlüde İnanç, Olçun Ümit Ünal, Emre Yılmaz, İlhan Hacıbekiroğlu, Sait Kitaplı, Özgür Tanrıverdi, Elif Şahin, Muhammed Fatih Sağıroğlu, Pembegül Yumuştutan, Seray Saray, Selahattin Çelik, Hayriye Şahinli, Azer Gökmen, Gizem Bakır Kahveci, Didem Divriklioğlu, Saadettin Kılıçkap
Journal of Clinical Medicine, Uluslararası, Wos, 2026, cilt 15, ss 2353-2353
DOI: 10.3390/jcm15062353
Özet
Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited. We report multicenter real-world outcomes from a large Turkish cohort. Methods: In this retrospective multicenter cohort study, we analyzed data from 24 oncology referral centers across Türkiye. Patients with histologically confirmed metastatic MTC who received systemic therapy between December 2011 and December 2024 were included. The primary endpoint was progression-free survival (PFS), assessed separately for first-line (PFS1) and second-line (PFS2) therapy. Overall survival (OS) and prognostic factors were evaluated using Kaplan–Meier and Cox proportional hazards analyses. Results: A total of 115 patients were included (median age 47.4 years; 63.5% male). In the first-line setting, vandetanib (47.8%) and cabozantinib (30.4%) were the most frequently used agents. Median PFS1 was 40.8 months with vandetanib and was not reached with cabozantinib; both were significantly superior to chemotherapy (median PFS1 4.9 months; log-rank p < 0.001). In the second-line setting, median PFS2 was not reached with cabozantinib and was 32.5 months with vandetanib. Sequential use of cabozantinib and vandetanib across the first two lines was associated with a median time to second progression of 114 months, compared with 39 months in patients receiving any other TKI combination (p = 0.003). Second-line use of cabozantinib or vandetanib was independently associated with improved OS (HR 0.40, 95% CI 0.16–0.98; p = 0.046). On multivariate analysis, younger age (HR 0.16, 95% CI 0.03–0.72; p = 0.017) and bone metastasis (HR 0.29, 95% CI 0.11–0.73; p = 0.009) were independent prognostic factors for OS. Conclusions: In this real-world cohort of patients with metastatic MTC, cabozantinib and vandetanib demonstrated durable efficacy across treatment lines, substantially outperforming alternative TKIs and chemotherapy. Sequential use of both approved aaMKIs was associated with prolonged disease control. These findings suggest a potential association between access to both agents and improved outcomes. They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating.