PMC7450975_01
Selpercatinib activity in patients with medullary thyroid cancer. Patient 1: magnetic resonance imaging scans of (A) right lateral and (B) left anterior liver metastatic lesions at baseline and after 22 months of treatment with selpercatinib of (C) right lateral and (D) left anterior in a heavily pretreated patient with RET-mutated medullary thyroid cancer. A rapid improvement in symptoms and a partial response were reported after two cycles of treatment, which deepened over time. Patient 2: computed tomography scans at baseline and after 4 months of treatment with selpercatinib of thorax (E, F, respectively) and mediastinum (G, H, respectively) showing metastatic disease in a patient with RET-mutated medullary thyroid cancer. Early disease control was achieved after two cycles of treatment.
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After two cycles of treatment, stable disease was observed (Fig 1E-H).
PMC7450975_02
Selpercatinib activity in patients with medullary thyroid cancer. Patient 1: magnetic resonance imaging scans of (A) right lateral and (B) left anterior liver metastatic lesions at baseline and after 22 months of treatment with selpercatinib of (C) right lateral and (D) left anterior in a heavily pretreated patient with RET-mutated medullary thyroid cancer. A rapid improvement in symptoms and a partial response were reported after two cycles of treatment, which deepened over time. Patient 2: computed tomography scans at baseline and after 4 months of treatment with selpercatinib of thorax (E, F, respectively) and mediastinum (G, H, respectively) showing metastatic disease in a patient with RET-mutated medullary thyroid cancer. Early disease control was achieved after two cycles of treatment.
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After two cycles of treatment, stable disease was observed (Fig 1E-H).
PMC7450975_03
Selpercatinib activity in patients with soft-tissue sarcoma. Patient 3: (A, C) computed tomography (CT) scans of the abdomen at baseline and (B, D) after 6 months of treatment with selpercatinib, revealing multiple paraspinal retroperitoneal and pelvic lesions in a patient with infantile myofibroma/hemangiopericytoma harboring an MYH10-RET fusion. A partial response was observed after one cycle of selpercatinib; after six cycles, the paraspinal lesion had completely resolved, and the patient regained lower extremity neurologic function. Patient 4: CT scans at baseline of (E) the lungs and (G) brain and after 8 months of treatment with selpercatinib of (F) the lungs and (H) brain in a patient with an SPECC1L-RET fusion-positive congenital mesoblastic nephroma and infantile fibrosarcoma. After two cycles of selpercatinib, a partial response was observed with a 41% tumor reduction, which deepened to 66% by cycle 8. Patient 5: CT scans (I, K) at baseline and (J, L) after 2 months of treatment with selpercatinib of the left foot in a patient with an NCOA4-RET fusion-positive lipofibromatosis. Selpercatinib treatment resulted in a significant decrease in tumor burden leading to improvements in gait and locomotion.
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Selpercatinib was initiated, and imaging after 2 months revealed a partial response by RECIST 1.1, with a 59% reduction in tumor volume and resolution of tumor infiltration of the metatarsals (Fig 2I-L).
PMC7450975_04
Selpercatinib activity in patients with soft-tissue sarcoma. Patient 3: (A, C) computed tomography (CT) scans of the abdomen at baseline and (B, D) after 6 months of treatment with selpercatinib, revealing multiple paraspinal retroperitoneal and pelvic lesions in a patient with infantile myofibroma/hemangiopericytoma harboring an MYH10-RET fusion. A partial response was observed after one cycle of selpercatinib; after six cycles, the paraspinal lesion had completely resolved, and the patient regained lower extremity neurologic function. Patient 4: CT scans at baseline of (E) the lungs and (G) brain and after 8 months of treatment with selpercatinib of (F) the lungs and (H) brain in a patient with an SPECC1L-RET fusion-positive congenital mesoblastic nephroma and infantile fibrosarcoma. After two cycles of selpercatinib, a partial response was observed with a 41% tumor reduction, which deepened to 66% by cycle 8. Patient 5: CT scans (I, K) at baseline and (J, L) after 2 months of treatment with selpercatinib of the left foot in a patient with an NCOA4-RET fusion-positive lipofibromatosis. Selpercatinib treatment resulted in a significant decrease in tumor burden leading to improvements in gait and locomotion.
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Selpercatinib was initiated, and imaging after 2 months revealed a partial response by RECIST 1.1, with a 59% reduction in tumor volume and resolution of tumor infiltration of the metatarsals (Fig 2I-L).
PMC7450975_05
Selpercatinib activity in patients with soft-tissue sarcoma. Patient 3: (A, C) computed tomography (CT) scans of the abdomen at baseline and (B, D) after 6 months of treatment with selpercatinib, revealing multiple paraspinal retroperitoneal and pelvic lesions in a patient with infantile myofibroma/hemangiopericytoma harboring an MYH10-RET fusion. A partial response was observed after one cycle of selpercatinib; after six cycles, the paraspinal lesion had completely resolved, and the patient regained lower extremity neurologic function. Patient 4: CT scans at baseline of (E) the lungs and (G) brain and after 8 months of treatment with selpercatinib of (F) the lungs and (H) brain in a patient with an SPECC1L-RET fusion-positive congenital mesoblastic nephroma and infantile fibrosarcoma. After two cycles of selpercatinib, a partial response was observed with a 41% tumor reduction, which deepened to 66% by cycle 8. Patient 5: CT scans (I, K) at baseline and (J, L) after 2 months of treatment with selpercatinib of the left foot in a patient with an NCOA4-RET fusion-positive lipofibromatosis. Selpercatinib treatment resulted in a significant decrease in tumor burden leading to improvements in gait and locomotion.
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Selpercatinib was initiated, and imaging after 2 months revealed a partial response by RECIST 1.1, with a 59% reduction in tumor volume and resolution of tumor infiltration of the metatarsals (Fig 2I-L).
Pharmacokinetics of selpercatinib in children. Plasma samples from three patients revealed that adequate plasma concentrations of selpercatinib were achieved (greater than RET wild-type concentration that inhibits 90% [IC90]), which were within the range seen in adult patients treated with the recommended dose of 160 mg in the LIBRETTO-001 trial. The gray area represents the 95% CIs for the median plasma concentrations observed in patients treated in the LIBRETTO-001 trial (red circles).
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The estimated steady-state maximum serum concentration (Cmax) and area under the serum concentration-time curve for 24 hours (AUC0-24) in these patients was similar to that of adults treated with selpercatinib 160 mg twice per day and consistent with significant (plasma concentrations greater than the concentration that inhibits 90% [IC90]) calculated RET target inhibition (Fig 3; data on file, Loxo Oncology, Stamford, CT).