The U.S. FDA recently granted conventional approval to Eli Lilly's selective RET kinase inhibitor Retevmo (selpercatinib) for the treatment of adults and children aged 2 years and older with advanced or metastatic RET fusion-positive thyroid cancer that requires systemic therapy and is resistant to radioactive iodine (RAI) if appropriate.
The conversion from accelerated approval to conventional approval is based on data from the Phase 1/2 LIBRETTO-001 trial (ClinicalTrials.gov identifier: NCT03157128), which included 65 patients with RET fusion-positive thyroid cancer who were RAI-resistant (if RAI is an appropriate treatment option) and either had not received systemic therapy or had received prior treatment. Study participants received selpercatinib until unacceptable toxicity or disease progression.
In 24 patients who had not received systemic therapy, the overall response rate (ORR) was 96% (95% CI, 79–100); the median duration of response (DOR) was not evaluable (NE) (95% CI, 42.8, NE). In 41 previously treated patients, the ORR was 85% (95% CI, 71–94); the median DOR was 26.7 months (95% CI, 12.1, NE).
Data from the open-label phase 1/2 LIBRETTO-121 trial (ClinicalTrials.gov identifier: NCT03899792) also support this approval. In 10 pediatric and adolescent patients with RET fusion-positive thyroid cancer, the ORR was 60% (95% CI, 26–88); 83% of responders had a response lasting at least 12 months.
Regarding safety, the most common adverse reactions (≥25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities (≥5%) were lymphopenia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium.
Retevmo is currently available in 40 mg and 80 mg capsules. New tablets in 40 mg, 80 mg, 120 mg, and 160 mg dose strengths have also been approved.
