Selpercatinib

Selpercatinib, sold under the brand name Retevmo, is a medication for the treatment of non-small cell lung cancer, medullary thyroid cancer, and other types of thyroid cancers in people whose tumors have an alteration (mutation or fusion) in a specific gene (RET or "rearranged during transfection").[1][2] It is taken by mouth.[2]

Selpercatinib
Clinical data
Trade namesRetevmo
Other namesLOXO-292
AHFS/Drugs.comProfessional Drug Facts
License data
Routes of
administration		By mouth
Drug classTyrosine kinase inhibitor
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
UNII
KEGG
Chemical and physical data
FormulaC29H31N7O3
Molar mass525.61 g·mol−1
3D model (JSmol)

The most common side effects include changes in laboratory tests (including increased liver enzymes, increased blood sugar, decreased white cell and platelet counts, decreased protein level, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium) dry mouth, diarrhea, high blood pressure, fatigue, edema, rash, and constipation.[1][2][3]

Selpercatinib is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing.[1][2] Before beginning treatment, the identification of a RET gene alteration must be determined using laboratory testing.[1]

Selpercatinib is the first therapy approved specifically for people with cancer and the RET gene alterations.[1]

Medical uses

Selpercatinib is a kinase inhibitor indicated for the treatment of

  • adults with non-small cell lung cancer (NSCLC) which has spread to other parts of the body (metastatic).[1][2][3]
  • adults and children 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC).[1][2][3]
  • adults and children 12 years of age and older with advanced or metastatic thyroid cancer who have received radioactive iodine that did not work or is no longer working.[1][2][3]

Adverse effects

Selpercatinib can cause serious side effects including liver toxicity, high blood pressure, heart rhythm changes due to prolongation of heart electrical activity (QT prolongation), bleeding, allergic reactions, impaired wound healing and harm to an unborn baby.[1][2][3]

Selpercatinib may cause harm to a developing fetus or a newborn baby.[1][2]

History

Selpercatinib was approved for use in the United States in May 2020.[1][4][5][3]

Selpercatinib was approved based on the results of the LIBRETTO-001 clinical trial (NCT03157128) involving 702 participants aged 15-92 years with each of the three types of tumors.[1][5][3] During the clinical trial, participants received 160 mg selpercatinib orally twice daily until disease progression or unacceptable toxicity.[1] The major efficacy outcome measures were overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage, and duration of response (DOR).[1] The trial was conducted at 84 sites in the United States, Canada, Australia, Hong Kong, Japan, South Korea, Singapore, Taiwan, Switzerland, Germany, Denmark, Spain, France, the United Kingdom, Italy and Israel.[3]

Efficacy for non-small cell lung cancer (NSCLC) was evaluated in 105 adult participants with rearranged during transfection (RET) fusion-positive NSCLC who were previously treated with platinum chemotherapy.[1] Sixty-four percent of the 105 participants with previously treated NSCLC, experienced complete or partial shrinkage of their tumors which lasted more than six months for 81% of them.[3] Out of 39 participants who had never undergone treatment, 84% experienced complete or partial shrinkage of their tumors which lasted more than six months for 58% of them.[3]

Efficacy for medullary thyroid cancer (MTC) was evaluated in participants 12 years of age and older with RET-mutant MTC .[1] The study enrolled 143 participants with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and participants with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib.[1] Sixty-nine percent of the 55 previously treated participants for MTC experienced complete or partial shrinkage of their tumors which lasted more than 6 months for 76% of them.[3] Out of 88 participants who had never undergone treatment with an approved drug, 73% experienced complete or partial shrinkage of their tumors which lasted more than six months for 61% of them.[3]

Efficacy for rearranged during transfection (RET) fusion-positive thyroid cancer was evaluated in participants 12 years of age and older.[1] The study enrolled 19 participants with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight participants with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy.[1] Seventy-nine percent of the 19 previously treated participants with thyroid cancer experienced complete or partial shrinkage of their tumors which lasted more than six months for 87% of them.[3] All eight participants who had not received therapy other than radioactive iodine therapy experienced complete or partial shrinkage of their tumors which lasted more than six months for 75 % of them.[3]

The US Food and Drug Administration (FDA) granted the application for selpercatinib priority review, orphan drug, and breakthrough therapy designations[1][6] and granted approval of Retevmo to Loxo Oncology, Inc., a subsidiary of Eli Lilly and Company.[1]

References
  1. "FDA Approves First Therapy for Patients with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion". U.S. Food and Drug Administration (FDA) (Press release). 8 May 2020. Retrieved 8 May 2020. This article incorporates text from this source, which is in the public domain.
  2. "Retevmo (selpercatinib) capsules, for oral use" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 8 May 2020.
  3. "Drug Trials Snapshots: Retevmo". U.S. Food and Drug Administration (FDA). 8 May 2020. Retrieved 1 June 2020. This article incorporates text from this source, which is in the public domain.
  4. "Retevmo: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 8 May 2020.
  5. "Lilly Receives U.S. FDA Approval for Retevmo (selpercatinib), the First Therapy Specifically for Patients with Advanced RET-Driven Lung and Thyroid Cancers" (Press release). Eli Lilly and Company. 8 May 2020. Retrieved 8 May 2020 – via PR Newswire.
  6. "FDA approves selpercatinib for lung and thyroid cancers with RET gene". U.S. Food and Drug Administration (FDA). 8 May 2020. Retrieved 11 May 2020. This article incorporates text from this source, which is in the public domain.

Further reading
  • Li AY, McCusker MG, Russo A, et al. (December 2019). "RET fusions in solid tumors". Cancer Treat. Rev. 81: 101911. doi:10.1016/j.ctrv.2019.101911. PMID 31715421.
  • Russo A, Lopes AR, McCusker MG, et al. (April 2020). "New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1)". Curr Oncol Rep. 22 (5): 48. doi:10.1007/s11912-020-00909-8. PMID 32296961.
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