PMC7608524_01
Clinical activity of selpercatinib (LOXO-292) in medullary thyroid cancer with extensive CNS metastases. (A) Magnetic resonance imaging (MRI) oblique axial cerebellar images of the patient's metastatic brain disease (left panel) before and (right panel) 8 weeks after the patient initiated treatment with selpercatinib. (B) Serial monitoring of calcitonin (blue circles) and carcinoembryonic antigen (CEA; red circles) during selpercatinib treatment. (C) MRI axial cerebellar and (D) sagittal thoracic spine images of the patient's metastatic disease (left panels) before and (right panels) 33 weeks after the patient initiated treatment with selpercatinib. (E) MRI axial brain images demonstrating a new caudate lesion after 17 months of therapy with selpercatinib (left panel) before and (right panel) after stereotactic radiosurgery (SRS). (F) RECIST plot indicating change in a target liver lesion according to RECIST, version 1.1. The first line indicates change from baseline. The second line indicates change from nadir.
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The patient achieved a partial response according to RECIST, version 1.1; at 8 months into treatment, disease progression developed (Fig 1). C5, T4, T8, L1 vertebrae and left posterior hilum;, nodular opacities in bilateral lungs; interlobular septal thickening suspicious for lymphangitic carcinomatosis; numerous hepatic lesions (largest, 7 cm in the dome of liver); >= 25 lesions in the brain and cerebellum (largest, 7 mm in the left cerebellar hemisphere; Fig 2A and 1C, left panels), and a 5-mm leptomeningeal nodule at the level of T11 (Fig 2D, left panel). Calcitonin and CEA levels measured 2,180 pg/mL and 12,312 ng/mL, respectively (Fig 2B).
Patient treatment timeline. CR, complete response; PD, progressive disease; PR, partial response; RT, radiation therapy; SRS, stereotactic radiosurgery; WBRT, whole-brain radiation therapy.
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C5, T4, T8, L1 vertebrae and left posterior hilum;, nodular opacities in bilateral lungs; interlobular septal thickening suspicious for lymphangitic carcinomatosis; numerous hepatic lesions (largest, 7 cm in the dome of liver); >= 25 lesions in the brain and cerebellum (largest, 7 mm in the left cerebellar hemisphere; Fig 2A and 1C, left panels), and a 5-mm leptomeningeal nodule at the level of T11 (Fig 2D, left panel). Calcitonin and CEA levels measured 2,180 pg/mL and 12,312 ng/mL, respectively (Fig 2B). Consistent with resolution of diarrhea, calcitonin levels decreased to < 2 pg/mL 3 months after therapy initiation (Fig 2B). MRI of the brain at 8 weeks demonstrated near-complete resolution of the previously identified brain metastases (Fig 2A, right panel), and MRI of the brain and spine at 33 weeks showed complete resolution of the brain metastases and the leptomeningeal nodule at the T11 level (Fig 2C and 2D, right panels). At 17 months, an MRI of the brain showed an isolated, new, 5-mm left caudate lesion that was treated with SRS (Fig 2E, left and right panels) with continuation of selpercatinib. CNS disease remained in response until 22 months, when several new brain lesions were found to have developed; these were managed with SRS (Fig 2).