Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors: a retrospective multi-center registry analysis
Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual out...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2022
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| In: |
Cancers
Year: 2022, Jahrgang: 14, Heft: 14, Pages: 1-15 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers14143405 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cancers14143405 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2072-6694/14/14/3405 
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| Verfasserangaben: | by Viktoria Florentine Koehler, Pia Adam, Carmina Teresa Fuss, Linmiao Jiang, Elke Berg, Karin Frank-Raue, Friedhelm Raue, Eva Hoster, Thomas Knösel, Hans-Ulrich Schildhaus, Thomas Negele, Udo Siebolts, Kerstin Lorenz, Stephanie Allelein, Matthias Schott, Christine Spitzweg and Matthias Kroiss on behalf of the German Study Group for Rare Malignant Tumors of the Thyroid and Parathyroid Glands |
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| 245 | 1 | 0 | |a Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors |b a retrospective multi-center registry analysis |c by Viktoria Florentine Koehler, Pia Adam, Carmina Teresa Fuss, Linmiao Jiang, Elke Berg, Karin Frank-Raue, Friedhelm Raue, Eva Hoster, Thomas Knösel, Hans-Ulrich Schildhaus, Thomas Negele, Udo Siebolts, Kerstin Lorenz, Stephanie Allelein, Matthias Schott, Christine Spitzweg and Matthias Kroiss on behalf of the German Study Group for Rare Malignant Tumors of the Thyroid and Parathyroid Glands |
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| 500 | |a medullary thyroid cancer; rearranged during transfection; variant; multi-tyrosine kinase inhibitor; survival; treatment outcome | ||
| 520 | |a Background: RET (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of RET status. The actual outcome of patients with RET-positive MTC treated with MKIs is ill described. Methods: We here retrospectively determined the RET oncogene variant status with a targeted DNA Custom Panel in a prospectively collected cohort of 48 patients with advanced MTC treated with vandetanib and/or cabozantinib at four German referral centers. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Results: In total, 44/48 (92%) patients had germline or somatic RET variants. The M918T variant was found in 29/44 (66%) cases. In total, 2/32 (6%) patients with a somatic RET variant had further somatic variants, while in 1/32 (3%) patient with a germline RET variant, additional variants were found. Only 1/48 (2%) patient had a pathogenic HRAS variant, and no variants were found in 3 cases. In first-line treatment, the median OS was 53 (95% CI (95% confidence interval), 32-NR (not reached); n = 36), and the median PFS was 21 months (12-39; n = 33) in RET-positive MTC patients. In second-line treatment, the median OS was 18 (13-79; n = 22), and the median PFS was 3.5 months (2-14; n = 22) in RET-positive cases. Conclusions: RET variants were highly prevalent in patients with advanced MTC. The treatment results in RET-positive cases were similar to those reported in unselected cohorts. | ||
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