The Food and Drug Administration (FDA) has granted accelerated approval to Gavreto™ (pralsetinib; Blueprint Medicines and Genentech) for the treatment of patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or with RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
Gavreto is a once-daily oral tyrosine kinase inhibitor designed to selectively and potently inhibit RET alterations. The approval was based on data from the phase 1/2 ARROW trial which evaluated the efficacy and safety of Gavreto in patients with RET-mutant MTC. The main efficacy outcome measures were the overall response rate (ORR) and duration of response (DOR).
Among 55 patients with RET-mutant metastatic MTC previously treated with cabozantinib and/or vandetanib, the ORR was 60% (95% CI, 46-73), of which 1.8% of patients had complete response and 58% had partial response. The median DOR was not reached (95% CI, 15.1 months, not estimable [NE]); 79% of patients had responses lasting 6 months or longer.
Among 29 patients with RET-mutant advanced MTC who were cabozantinib and vandetanib treatment-naïve, the ORR was 66% (95% CI, 46-82), of which 10% of patients had complete response and 55% had partial response. The median DOR was not reached (95% CI, NE, NE); 84% of patients had responses lasting 6 months or longer.
Among 9 patients with RET fusion-positive thyroid cancer, the ORR was 89% (95% CI, 52-100), of which none achieved a complete response and 89% had partial response. The median DOR was not reached (95% CI, NE, NE); all patients had responses lasting 6 months or longer.
As for safety, the most common adverse reactions reported included constipation, hypertension, fatigue, musculoskeletal pain and diarrhea.
“Traditionally, we have treated patients with RET-altered thyroid cancers with multikinase inhibitors, non-selective therapies with modest efficacy and clinically significant side effects,” said Mimi Hu, MD, professor in the Department of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center, and an investigator on the ARROW trial. “The FDA approval of pralsetinib (Gavreto), a once-daily RET-targeted therapy, advances the standard of care for these patients.”
Gavreto is also indicated for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer as detected by an FDA approved test.
For more information visit gavreto.com.
1. FDA approves pralsetinib for RET-altered thyroid cancers. [press release]. Silver Spring, MD: US Food and Drug Administration; December 1, 2020.
2. Blueprint Medicines announces FDA approval of Gavreto™ (pralsetinib) for the treatment of patients with advanced or metastatic ret-mutant and ret fusion-positive thyroid cancer. [press release]. Cambridge, MA: Blueprint Medicines Corporation; December 1, 2020.
3. Gavreto™ [package insert]. Cambridge, MA: Blueprint Medicines Corporation; 2020.