Selpercatinib Safe, Effective for Medullary Thyroid Cancer With RET Mutation

In a phase 1/2 trial, selpercatinib was shown to be effective, with manageable safety, in patients with RET-mutant medullary thyroid cancer, whether or not they had received previous therapy with vandetanib or cabozantinib (N Engl J Med. 2020;383:825-835).

RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown,” explained lead investigator Lori J. Wirth, MD, Massachusetts General Hospital, Boston, and colleagues.

Eligible patients included those with RET-positive medullary thyroid cancer who had or had not previously received treatment with vandetanib or cabozantinib, as well as patients with pre-treated RET fusion-positive thyroid cancer.

The primary end point was objective response (complete or partial), as determined by an independent review committee, while secondary end points included the duration of response, progression-free survival (PFS), and safety.

Of the patients enrolled, 55 had previously received vandetanib, cabozantinib, or both; of these patients, 69% had a response (95% CI, 55-81). Meanwhile, 73% (95% CI, 62-82) of the 88 patients who had not received prior treatment with vandetanib or cabozantinib had a response.

The 1-year PFS was 82% (95% CI, 69-90) and 92% (95% CI, 82-97), respectively. 

Among the 19 patients with pre-treated RET fusion-positive thyroid cancer, 79% (95% CI, 54-94) had a response, and the 1-year PFS was 64% (95% CI, 37-82).

The most common grade ≥3 adverse events (AEs) included hypertension (21%), increased alanine aminotransferase (11%), increased aspartate aminotransferase (9%), hyponatremia (8%), and diarrhea (6%). Of note, 2% of patients discontinued selpercatinib due to drug-related AEs.

“In this phase 1/2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment,” concluded Dr Wirth et al.—Alexandra Graziano

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