Key Objectives With Selpercatinib Use in RET Fusion-Positive Thyroid Cancer

Vivek Subbiah discusses the phase 1/2 LIBRETTO-001 study which sought to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of selpercatinib in patients with advanced solid tumors.

In an interview with Targeted OncologyTM, Vivek Subbiah, an associate professor in the Investigational Cancer Therapeutics department, and medical director of the Clinical Center for Targeted Therapy, Cancer Medicine division at The University of Texas MD Anderson Cancer Center, explains the structure and end points of the LIBRETTO-001 trial (NCT03157128).

The phase 1/2 LIBRETTO-001 study sought to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of selpercatinib (LOXO-292). Participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation were administered selpercatinib orally.

Findings showed durable efficacy in RET-altered thyroid tumors heavily pretreated and treatment-naïve patients. Overall response rate (ORR) was 79% in patients with previously treated RET fusion-positive thyroid cancer and in the treatment-naïve group, response rate was 100%, according to Subbiah. According to the findings of that response rate, 71% were ongoing and 64% stayed progression-free. The approval of selpercatinib capsules for the treatment of thyroid cancer harboring RET alterations by the FDA was supported by these findings.


0:08 | A total of 441 patients with RET fusion-positive cancers were enrolled in the study as of the data cutoff Of March 19, 2021. In this specific presentation, I discussed the 38 patients who have RET fusion-positive cancer, excluding those with lung or thyroid as data from these patients have been previously published. The efficacy evaluable population included 32 patients who enrolled on or before September 19, 2020, long enough to allow a 6-month follow-up after the first dose of selpercatinib. The patients were required to be at least 12 years of age with a diagnosis of an advanced or metastatic solid tumor and an equal performance status of 0 to 2.

The primary endpoint was ORR, and secondary end points included duration of response, progression-free survival, safety, and others. RET fusions occur predominantly in 1% to 2% of lung cancers, and 10% to 20% of thyroid cancers. They have a very low frequency in an increasing number of diverse cancers like pancreatic cancer, salivary gland cancer, and colorectal cancer. The therapeutic relevance of RET fusions occurring outside the lung and thyroid has not been well established, and that was the purpose of this analysis.