FDA D.I.S.C.O. Burst Edition: FDA approval of Retevmo (selpercatinib) for advanced or metastatic RET fusion-positive thyroid cancer
Regulatory approval: On May 29, 2024, the FDA granted accelerated approval to selpercatinib (Retevmo) for pediatric patients aged ≥2 years with (1) advanced/metastatic RET-mutant medullary thyroid cancer requiring systemic therapy; (2) advanced/metastatic RET fusion–positive thyroid cancer requiring systemic therapy that is radioactive iodine–refractory (if RAI is appropriate); and (3) locally advanced/metastatic RET fusion–positive solid tumors with progression after prior systemic therapy or no satisfactory alternatives. Approval was supported by LIBRETTO-121 (single-arm), with confirmed ORR 48% and median DoR not reached.
FDA D.I.S.C.O. Burst Edition: Retevmo (selpercatinib) in pediatric RET-altered cancers (regulatory approval)
On May 29, 2024, the FDA granted accelerated approval to selpercatinib (Retevmo) for pediatric patients ≥2 years with RET-altered malignancies, as detected by an FDA-approved test, who require systemic therapy:
- Advanced or metastatic medullary thyroid cancer with a RET mutation
- Advanced or metastatic thyroid cancer with a RET gene fusion that is radioactive iodine–refractory (if radioactive iodine is appropriate)
- Locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on/following prior systemic treatment or have no satisfactory alternative options
The FDA noted this is the first approval of a targeted therapy for pediatric patients <12 years with RET alterations. Selpercatinib previously received accelerated approvals for certain thyroid cancer indications in adults and pediatric patients ≥12 years, and for the solid tumor indication in adults.
Supporting evidence
Efficacy was evaluated in LIBRETTO-121, an international, single-arm, multi-cohort trial. In the primary efficacy population (n=25, ages 2–20) with locally advanced/metastatic RET-activated solid tumors, the confirmed overall response rate (ORR) by blinded independent review was 48%. Median duration of response (DoR) was not reached; 92% of responders remained in response at 12 months.
Safety
Common adverse reactions (>25%) included musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. Common grade 3/4 lab abnormalities (>5%) included decreased calcium, hemoglobin, and neutrophils.