Selpercatinib Wins FDA Traditional Approval for RET Fusion-Positive Thyroid Cancer

• The FDA has granted traditional approval to selpercatinib (Retevmo) for the treatment of adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine (RAI)-refractory.
• Selpercatinib was granted accelerated approval in this population in 2020.
• The approval is supported by findings from the LIBRETTO-001 (NCT03157128).

Selpercatinib has received traditional approval from the FDA for the treatment of adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are RAI-refractory.¹

"We have gotten a little bit spoiled with the results from selpercatinib, and I think that there's a hope that we often can anticipate. This is a class of drugs that we have seen and used in lung cancer, melanomas, thyroid cancer, and many other cancers," Marcia S. Brose, MD, PhD, FASCO, professor in the Department of Medical Oncology Sidney Kimmel Medical College Thomas Jefferson University, professor and vice chair in the Department of Medical Oncology Jefferson Northeast, chief of Cancer Services, Sidney Kimmel Cancer Center-Jefferson Northeast, associate director of Community Based Clinical Research, and SKCC chair of Hematology/Oncology, Jefferson Torresdale Hospital, told Targeted Oncology^TM in an interview.

The drug was initially granted accelerated approval in 2020 and its efficacy was verified in the LIBRETTO-001 study. The overall response rates (ORR) were 85% (95% CI, 71%-94%) in patients who were previously treated with systemic therapy (n = 41) and 96% (95% CI, 79%-100%) in the patients who were naive to systemic therapy (n = 24). The median durations of response (DOR) were 26.7 months (95% CI, 12.1-not evaluable [NE]) and NE (95% CI, 42.8-NE) in the previously treated and systemic treatment-naive populations, respectively.

Additional evidence came from the LIBRETTO-121 (NCT03899792) study and included ORR and DOR data from 10 pediatric and young adult patients with RET fusion-positive thyroid cancer. The ORR was 60% (95% CI, 26%-88%), and 83% of patients had an observed duration of response 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 decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, decreased sodium, and decreased calcium.

In May 2024, the FDA also granted accelerated approval to selpercatinib for the treatment of pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer with a RET mutation, advanced or metastatic thyroid cancer with a RET fusion, and locally advanced or metastatic solid tumors with a RET gene fusion. This approval was supported by the LIBRETTO-121 trial.²

REFERENCES:

1. FDA approves selpercatinib for RET fusion-positive thyroid cancer. News release. FDA. June 12, 2024. Accessed June 12, 2024. https://tinyurl.com/3eaamaxu

2. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. News release. FDA. May 29, 2024. Accessed June 12, 2024. https://tinyurl.com/3ykektts