Selpercatinib

Initial US Approval

Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test.¹

Adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.¹

Adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).¹

Adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options¹
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Selpercatinib: Dose Reduction

Key Inclusion Criteria: Eligible study participants included patients with advanced or metastatic RET fusion-positive NSCLC who had progressed on platinum-based chemotherapy and patients with locally advanced (stage III who were not candidates for surgical resection or definitive chemoradiation) or metastatic NSCLC without prior systemic therapy.¹
Treatment: Selpercatinib 160 mg orally twice daily until unacceptable toxicity or disease progression.¹

Selpercatinib: Efficacy Data

Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), constipation (33%), rash (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%).¹
Common Laboratory Abnormalities (≥30%): The most frequently reported laboratory abnormalities were increased AST (59%), decreased calcium (59%), increased ALT (56%), decreased albumin (56%), increased glucose (53%), decreased lymphocytes (52%), increased creatine (47%), decreased sodium (42%), increased alkaline phosphatase (40%), decreased platelets (37%), increased total cholesterol (45%), increased potassium (34%), decreased glucose (34%), decreased magnesium (33%), and increased bilirubin (30%).¹
Dosage Interruption Due to AEs: 64%¹
Dosage Reductions Due to AEs: 41%¹
Permanent Discontinuation Due to AEs: 8%¹

Selpercatinib: Most Common Adverse Events of Grade 3 or 4

RETEVMO (selpercatinib). Prescribing information. Eli Lilly and Company; 2022. https://pi.lilly.com/us/retevmo-uspi.pdf?s=pi
Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med. 2020;383(9):813-824. doi:10.1056/NEJMoa2005653
Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion-positive non-small-cell lung cancer: updated safety and efficacy from the registrational LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2023;41(2):385-394. doi:10.1200/JCO.22.00393
Occurrence and management of selpercatinib- and pralsetinib-related AEs in patients with RET fusion-positive mNSCLC. Targeted Oncology. January 20, 2023. Accessed November 18, 2024. https://www.targetedonc.com/view/occurrence-and-management-of-selpercatinib--and-pralsetinib-related-aes-in-patients-with-ret-fusion-positive-mnsclc
Nardo M, Gouda MA, Nelson BE, et al. Strategies for mitigating adverse events related to selective RET inhibitors in patients with RET-altered cancers. Cell Rep Med. 2023;4(12):101332. doi:10.1016/j.xcrm.2023.101332