US regulators have approved Eli Lilly's Retevmo (selpercatinib) as the first therapeutic specifically designed for patients with advanced RET-driven lung and thyroid cancers.

Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signalling and uncontrolled cell growth, and have been identified in a variety of cancers.

The US Food and Drug Administration has given its seal of approval for use of the drug to treat adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and adult and paediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.

The selective RET kinase inhibitor was cleared under the regulator's accelerated approval process on the back of data from the LIBRETTO-001 Phase I/II trial, which had endpoints of objective response rate (ORR) and duration of response (DoR).

Therefore, continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

"In the clinical trial, we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases," said Alexander Drilon, acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator for LIBRETTO-001.

"The approval of selpercatinib marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy."

"RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers. For patients living with these cancers, the approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET," added Lori Wirth, medical director of head and neck cancers, Massachusetts General Hospital Cancer Center.

"Based on the published data for this new medicine, as well as my personal experience treating patients, this may be a good treatment option."

On the safety side, serious hepatic adverse reactions occurred in 2.6% of patients treated with Retevmo. Increased AST occurred in 51% of patients, including Grade 3 or 4 events in 8% and increased ALT occurred in 45% of patients, including Grade 3 or 4 events in 9%. Also, hypertension was observed in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one (0.1%) patient.