Selpercatinib shows promise in RET-mutant medullary thyroid cancer
Selective RET inhibition with selpercatinib has demonstrated durable efficacy with low-grade toxicity in medullary thyroid cancer patients harbouring RET mutation, according to the results of a phase I–II trial.
The study included three patient cohorts: 55 with RET-mutant medullary thyroid cancer previously treated with vandetanib, cabozantinib, or both (first); 88 with RET-mutant medullary thyroid cancer not previously treated with either drug (second); and 19 with RET fusion–positive previously treated thyroid cancer (third).
Patients who were enrolled in the first phase received selpercatinib at doses ranging from 20 mg once daily to 240 mg twice daily, while those enrolled in the second phase received the recommended dose of 160 mg twice daily. The drug was given orally (capsule or liquid) and continuously, in 28-day cycles, until disease progression, death, unacceptable toxic effects, or withdrawal.
In the first cohort, 69 percent (95 percent confidence interval [CI], 55–81) of patients achieved response (complete or partial). The 1-year progression-free survival was 82 percent (95 percent CI, 69–90).
The respective response and 1-year progression-free survival rates were 73 percent (95 percent CI, 62–82) and 92 percent (95 percent CI, 82–97) in the second cohort, and 79 percent (95 percent CI, 54–94) and 64 percent (95 percent CI, 37–82) in the third cohort.
Common adverse events of grade ≥3 were hypertension (21 percent), increased alanine aminotransferase level (11 percent), increased aspartate aminotransferase level (9 percent), hyponatremia (8 percent), and diarrhoea (6 percent).
Drug-related adverse events led to treatment discontinuation in 12 patients (2 percent).