Selpercatinib Receives FDA Approval Across RET-Positive Cancers

For disease that progressed during or after systemic treatment, or has no satisfactory alternative treatment, in locally advanced or metastatic RET fusion-positive solid tumours (arising in organs or tissues) in adults, selpercatinib (Retevmo, Eli Lilly and Company) received accelerated FDA (US Food and Drug Administration) approval on 21 September 2022.

In 2020, selpercatinib received accelerated FDA approval for RET-positive lung and thyroid cancers; on 21 September, its non-small cell lung cancer approval became regular approval. The latest decision expands its use across RET-positive tumour types, including pancreatic and colorectal cancer.

What Is a RET Fusion?

The RET gene is a proto-oncogene that instructs production of a protein involved in intracellular signalling. This protein appears necessary for normal development of several nerve cells, including intestinal nerves and the autonomic nervous system, which controls involuntary functions such as heart rate. The RET protein is also needed for normal kidney development and sperm production (spermatogenesis). Loss-of-function RET mutations are associated with Hirschsprung disease, while mutations giving the gene different functions are associated with various human cancers. RET fusion is one of these genetic changes. RET alterations occur in about 1-2% of patients with lung cancer. In conclusion, RET fusion is a rare cancer-driving genetic alteration found across several cancer types.

RET Fusion Joins the Pan-Cancer Biomarkers

Examples of cancer treatment independent of the organ or tissue of origin are increasing. This approval confirms that RET fusion is now one of the genetic biomarkers guiding treatment irrespective of the organ of origin.

Approval was based on the phase 1/2 LIBRETTO-001 study, which evaluated 41 patients with RET fusion-positive tumours. Thirty-seven (90%) had received systemic treatment, and nearly a third had received three or more lines. The primary efficacy measures were overall response rate and response duration.

Among 41 patients, the overall response rate was 44%, with a median response duration of 24.5 months. Responses lasted at least 6 months in 67% of patients.

This approval highlights growing tumour-agnostic treatment options and the importance of routine comprehensive genomic testing for patients with advanced cancers across a wide range of tumour types.

The most common cancers in the study were pancreatic adenocarcinoma (27%), colorectal cancer (24%) and salivary gland cancer (10%).

The most common selpercatinib-related adverse effects were oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea and headache.

The recommended selpercatinib dose, based on body weight, is 120 mg orally twice daily for patients weighing under 50 kilo, or 160 mg twice daily for those weighing 50 kilo or more.