On September 21, 2022, the FDA accelerated the approval of selpercatinib (Retevmo; Eli Lilly), a RET kinase inhibitor, for the treatment of locally advanced or metastatic solid tumors with a RET gene fusion in patients whose disease has progressed while or after receiving systemic treatment or who have no alternative treatment options.
On the same day, the FDA granted regular approval to selpercatinib for the treatment of locally advanced or metastatic RET fusion–positive non–small-cell lung cancer (NSCLC), as detected by an FDA-approved test. On May 8, 2020, the FDA granted accelerated approval to selpercatinib for the NSCLC indication based on overall response rate (ORR) and duration of response (DOR) in 144 patients in the LIBRETTO-001 clinical trial.
The FDA concomitantly approved the Oncomine Dx Target Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.
Selpercatinib was previously approved for the treatment of advanced or metastatic RET-positive medullary thyroid cancer in patients aged ≥12 years, and for the treatment of advanced or metastatic RET-positive thyroid cancer, as detected by an FDA-approved test, in patients aged ≥12 years who require systemic therapy and have radioactive iodine-refractory disease.
These approvals were based on the efficacy results of the multicenter, multicohort, open-label LIBRETTO-001 trial. For the solid-tumor indication, the efficacy of selpercatinib was evaluated in 41 patients with RET-positive solid tumors, with the exception of NSCLC and thyroid cancer, whose disease progressed while or after receiving systemic therapy or who had no alternative treatment options. The patients received selpercatinib until their disease progressed or they had unacceptable toxicity.
The major efficacy measures of the study were ORR and DOR, as determined by a blinded Independent Review Committee. For the solid-tumor indication, the ORR was 44% (95% confidence interval [CI], 28-60) and the DOR was 24.5 months (95% CI, 9.2-not estimable). The tumor types that showed responses included pancreatic adenocarcinoma, soft-tissue sarcoma, bronchial carcinoid, cholangiocarcinoma, and colorectal, salivary, breast, ovarian, small intestine, and unknown primary cancers.
For the NSCLC indication, efficacy was demonstrated in 316 patients with locally advanced or metastatic RET-positive NSCLC. The patients received selpercatinib until disease progression or unacceptable toxicity. Of 69 treatment-naïve patients with RET-positive NSCLC, the ORR was 84% (95% CI, 73-92) and the DOR was 20.2 months (95% CI, 13-not estimable). Of 247 patients who previously received platinum-based chemotherapy, the ORR was 61% (95% CI, 55-67) and the DOR was 28.6 months (95% CI, 20-not estimable).
The most common (≥25%) adverse reactions include edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
The full approval of the NSCLC indication was based on data from an additional 172 patients and 18 months of further follow-up to evaluate the durability of the response.
The recommended dose of selpercatinib is based on body weight and is 120 mg orally twice daily for patients who weigh <50 kg and 160 mg orally twice daily for patients who weigh ≥50 kg.
