Metastatic medullary thyroid carcinoma (MTC) with somatic variants of unknown significance in the RET gene can respond to treatment with pralsetinib, according to a recently published case report in the European Thyroid Journal.
The case involved a 48-year-old man with liver metastases that were identified during a cholecystectomy. Computer tomography and magnetic resonance imaging revealed a primary thyroid tumor with metastases in the liver, bone, lung, lymph nodes, and brain.
Results of a liver biopsy revealed metastatic MTC. As the patient had no family history and no evidence of a germline mutation of the RET gene, the attending physicians performed an additional next-generation sequencing (NGS), showing variants of unknown significance in the RET gene.
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On account of the allele frequency of the missense variant, a second NGS panel was performed on tumor DNA, revealing a germline RET mutation.
Sporadic forms account for over 75% of MTCs, with RET mutations being found in approximately 50% of cases of sporadic MTC.
There were no significant changes in disease status during the following 6 months; however, 9 months after diagnosis, the patient presented with symptoms produced by increased calcitonin production and Response Evaluation Criteria in Solid Tumors progression. In consequence, the case was discussed in the local molecular tumor board, where initiation of RET inhibition treatment with pralsetinib was decided.
Pralsetinib received recent US Food and Drug Administration approval for the treatment of both lung and thyroid cancer with RET mutations. Phase 1 and 2 studies in patients with MTC showed a response rate superior to 70%. After beginning treatment in January 2021, the patient remains alive to this date, showing a clear clinical benefit from treatment.
“This case illustrates the value of molecular tumor boards where multidisciplinary discussions can lead to select targeted therapies that benefit patients. Moreover, the tumor response to a highly specific RET inhibitor suggests that this patient’s RET indel is causative of MTC,” the authors concluded.
Hescot S, Masliah-Planchon J, du Rusquec P, et al. Significant response to pralsetinib in a medullary thyroid cancer harboring double ret variants of unknown significance. Eur Thyroid J. Published online September 27, 2022. doi:10.1530/etj-22-0044