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Case Reports
. 2020 Apr 14:4:PO.19.00401.
doi: 10.1200/PO.19.00401. eCollection 2020.

Activity of the Highly Specific RET Inhibitor Selpercatinib (LOXO-292) in Pediatric Patients With Tumors Harboring RET Gene Alterations

Michael V Ortiz  1 , Ulrike Gerdemann  2 , Sandya Govinda Raju  3 , Dahlia Henry  3 , Steve Smith  4 , S Michael Rothenberg  3 , Michael C Cox  4 , Stéphanie Proust  5 , Julia Glade Bender  1 , A Lindsay Frazier  2 , Peter Anderson  6 , Alberto S Pappo  7
Affiliations
Case Reports

Activity of the Highly Specific RET Inhibitor Selpercatinib (LOXO-292) in Pediatric Patients With Tumors Harboring RET Gene Alterations

Michael V Ortiz et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Sandya Govinda RajuEmployment: Loxo OncologyDahlia HenryEmployment: Loxo Oncology Stock and Other Ownership Interests: Loxo Oncology, Allergan, Axovant Sciences, Palatin TechnologiesSteve SmithConsulting or Advisory Role: Various, Loxo Oncology Patents, Royalties, Other Intellectual Property: Various patents and applications Travel, Accommodations, Expenses: VariousS. Michael RothenbergEmployment: Loxo Oncology Stock and Other Ownership Interests: Loxo OncologyMichael C. CoxEmployment: Bayer, Loxo Oncology, Merck KGaA, Amgen, Day One Biopharmaceuticals Stock and Other Ownership Interests: Loxo Oncology, Bayer, Merck KGaA, Amgen, Day One Biopharmaceuticals Patents, Royalties, Other Intellectual Property: US patent 62/318,041 issued to Loxo Oncology (Inst)Julia Glade BenderConsulting or Advisory Role: AbbVie (Inst) Research Funding: Celgene (Inst), Merck (Inst), Pfizer (Inst), Amgen (Inst), Ignyta (Inst), Bristol-Myers Squibb (Inst), Eisai (Inst), Novartis (Inst), Eli Lilly (Inst), Loxo Oncology (Inst), Genentech (Inst) Travel, Accommodations, Expenses: Novartis, Amgen, Merck, Bayer, Genentech Uncompensated Relationships: SpringWorks Therapeutics, Bristol-Myers SquibbA. Lindsay FrazierStock and Other Ownership Interests: Decibel Therapeutics Consulting or Advisory Role: Decibel TherapeuticsPeter AndersonStock and Other Ownership Interests: Healios Consulting or Advisory Role: Enlivity Patents, Royalties, Other Intellectual Property: Patent for glutamine and trehalose compositions; priority date 13 September 2013; App 14/470, 545, filed August 27, 2014; patent 61/878,084 issued December 26, 2017 Other Relationship: EnlivityAlberto S. PappoHonoraria: Bayer, Roche Consulting or Advisory Role: Merck, Loxo Oncology/Bayer, EUSA Pharma No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
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.
FIG 2.
FIG 2.
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.
FIG 3.
FIG 3.
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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