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The FDA on Tuesday to include advanced or metastatic RET-mutant medullary thyroid cancer and radioactive iodine (RI)-refractory RET fusion-positive thyroid cancer.

Support for the approval, in adults and children age 12 and older, was based on findings from the phase I/II ARROW trial, a multi-cohort open-label study for patients whose tumors carry RET gene alterations.

In patients with RET-mutant medullary thyroid cancer, treatment with the oral RET inhibitor pralsetinib yielded an overall response rate (ORR) of 60% (95% CI 46%-73%) in 55 patients who had previously been treated with either vandetanib (Caprelsa) or cabozantinib (Cometriq), and 66% (95% CI 46%-82%) in 29 patients who were naïve to the two multi-kinase inhibitors. Among responders in the two groups, 79% and 84%, respectively, had responses of 6 months or more.

In nine patients with RI-refractory RET fusion-positive thyroid cancer, the ORR reached 89% (95% CI 52-100), with all eight patients who responded having responses of at least 6 months.

"Traditionally, we have treated patients with RET-altered thyroid cancers with multi-kinase inhibitors, non-selective therapies with modest efficacy and clinically significant side effects. The FDA approval of pralsetinib (Gavreto), a once-daily RET-targeted therapy, advances the standard of care for these patients," ARROW investigator Mimi Hu, MD, of MD Anderson Cancer Center in Houston, said in a from drugmaker Blueprint Medicines. "As a clinical researcher with a focus on thyroid cancer, I am encouraged by the safety profile and durable responses shown by Gavreto in RET-altered thyroid cancers in both treatment-naïve and previously treated patients."

Common adverse events (≥25%) of any grade in the trial included constipation, diarrhea, fatigue, hypertension, and musculoskeletal pain. Common grade 3/4 hematologic events (≥2%) included decreases in calcium, hemoglobin, lymphocytes, neutrophils, phosphate, platelets, and sodium; as well as increases in liver enzymes and alkaline phosphatase.

Recommended dosing of pralsetinib is 400 mg once daily on an empty stomach (no food for 2 hours before taking the drug and 1 hour after).

The thyroid cancer indication is the second approval for pralsetinib, following the drug's earlier this year, which was also based on findings from ARROW.

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