FDA Approves Selpercatinib for RET Fusion–Positive Thyroid Cancer
On June 12, 2024, the U.S. Food and Drug Administration (FDA) granted traditional approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-ret-fusion-positive-thyroid-cancer) to selpercatinib (Retevmo®) for adult and pediatric patients aged 2 years and older with advanced or metastatic RET fusion–positive thyroid cancer that requires systemic therapy but is refractory to radioactive iodine (RAI), if RAI is appropriate.
Selpercatinib received (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions) accelerated approval for the indication for patients aged 12 years and older in 2020.
Efficacy was evaluated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, muticohort clinical trial in 65 patients with RET fusion–positive thyroid cancer. Participants were divided into an RAI-refractory (if RAI was an appropriate treatment option) and systemic therapy–naïve cohort (n = 24) and patients who were previously treated (n = 41), in separate cohorts.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The ORR was 85% (95% CI = 71%, 94%) in the previously treated patients and 96% (95% CI = 79%, 100%) in the systemic therapy–naïve patients. Median DOR was 26.7 months (95% CI = 12.1, not evaluable [NE]) in the previously treated patients and NE (95% CI = 42.8, NE) in the systemic therapy–naïve patients.
Supportive evidence included ORR and DOR data from 10 pediatric and young adult patients with RET fusion–positive thyroid cancer treated in LIBRETTO-121 (J2G-OX-JZJJ; NCT03899792), an international, single-arm, multicohort clinical trial of selpercatinib in pediatric and young adult patients with advanced RET-altered solid tumors. The ORR was 60% (95% CI = 26%, 88%), and 83% had an observed duration of response of at least 12 months.
In the drug’s clinical trials, the most common adverse reactions reported in at least 25% of patients were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities reported in at least 5% of patients were decreased lymphocytes, increased ALT and AST, decreased sodium, and decreased calcium.
The recommended selpercatinib dose for pediatric patients aged 2 to less than 12 years is based on body surface area. It is based on weight for patients aged 12 years and older. See the prescribing information (https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218160s001lbl.pdf) for specific dosing information.
The applicant used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) to facilitate FDA’s review. FDA granted the application breakthrough designation and orphan drug designation. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).