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Two studies show efficacy of selpercatinib in RET-altered thyroid cancers and in patients with RET fusion-positive solid tumors other than lung or thyroid ones
Two new studies point out for a broad efficacy of selpercatinib, a first-in-class, highly selective RET kinase inhibitor, in a range of tumors: a phase 1–2 trial of selpercatinib published on The New England Journal of Medicine has demonstrated durable efficacy in patients with RET-mutant medullary thyroid cancer; another paper on The Lancet Oncology showed a clinically meaningful activity in a RET fusion-positive tumor-agnostic population.
The first study enrolled 531 patients with RET-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated RET fusion–positive thyroid cancer; patients who were enrolled in the phase 1 dose-escalation portion of the trial received selpercatinib at doses ranging from 20 mg once daily to 240 mg twice daily, patients in the phase 2 portion received the recommended dose of 160 mg twice daily. Results showed an objective response ranging from 69% to 79% (in patients who had previously received vandetanib, cabozantinib or both or patients with previously treated RET fusion–positive thyroid cancer, respectively) and a 1-year progression-free survival ranging from 64 to 92% (in patients with previously treated RET fusion–positive thyroid cancer or patients who had not previously received vandetanib or cabozantinib, respectively), with a durable efficacy and mainly low-grade toxic effects.
The second study, the LIBRETTO-001 trial, is an ongoing phase 1/2, single-group, open-label, basket trial of selpercatinib in patients aged 18 years and older (or ≥12 years, where permitted by regulatory authorities) with RET-altered cancers, enrolled at 30 sites across eight countries. Selpercatinib was orally administered in a continuous 28-day cycle; patients enrolled in the phase 1 dose-escalation portion received between 20 mg once daily or 20–240 mg twice daily; the phase 2 recommended dose was 160 mg twice daily. Of the 41 efficacy-evaluable patients, the objective response rate was 43.9%, with no treatment related death and a safety profile consistent with that observed in other indications. As authors conclude, «Selpercatinib showed clinically meaningful activity in the RET fusion-positive tumor-agnostic population, with non-lung or thyroid advanced solid tumors. Comprehensive genomic testing that includes RET fusions will be crucial for identifying patients who might benefit from selpercatinib».