December 1, 2020 - The FDA has approved pralsetinib for the treatment of select patients with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.
The FDA has approved pralsetinib (Gavreto) for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are refractory to radioactive iodine.1
The regulatory decision was based on data from the multicenter, open label, multicohort phase 1/2 ARROW trial (NCT03037385), where the safety and efficacy of pralsetinib was evaluated in patients with RET fusion–positive non–small cell lung cancer (NSCLC), RET-mutated MTC, RET fusion–positive thyroid cancer, and other RET-altered solid tumors.
Investigators prospectively identified these alterations in local laboratories through the use of next-generation sequencing, fluorescence in situ hybridization, or other tests. The main efficacy outcome measures evaluated in the trial consisted of overall response rate (ORR) and duration of response (DOR) per a blinded independent review committee via RECIST v1.1 criteria.
Results showed that among 55 patients with advanced or metastatic RET-mutant MTC who had received prior cabozantinib (Cabometyx) or vandetanib, pralsetinib elicited an ORR of 60% (95% CI, 46%-73%). Additionally, 79% percent of responders experienced responses that persisted for 6 months or longer.
Among 29 patients with RET-mutant MTC who did not receive previous treatment with cabozantinib or vandetanib, pralsetinib induced an even higher ORR of 66% (95% CI, 46%-82%). Notably, 84% of these patients had responses that persisted for 6 months or longer. Among 9 patients with RET fusion–positive thyroid cancer who were also refractory to radioactive iodine, the ORR reported with pralsetinib was 89% (95% CI, 52%-100%). Here, all responders experienced responses that lasted for 6 months or longer.
"We are proud to partner with Blueprint Medicines to bring this important new option to people with certain types of RET-altered thyroid cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, commented in email correspondence. “[Pralsetinib] is now approved across multiple RET-altered tumor types, underscoring our commitment to advancing personalized healthcare with treatments that target the underlying biology of each person’s cancer.”
With regard to safety, the most frequently reported adverse effects reported in 25% of patients or more included constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea.
Grade 3/4 laboratory abnormalities that were reported in 2% or. more of participants comprised decreased lymphocytes, reduced neutrophils, decreased hemoglobin, reduced phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, a reduction in platelets, and increased alkaline phosphatase.
Previously, in September 2020, the FDA approved pralsetinib for the treatment of adult patients with metastatic RET fusion–positive NSCLC, as identified via an FDA-approved test. Again, the decision was based on data from ARROW, where the agent was found to elicit durable clinical responses in this patient population.2
Specifically, results showed that pralsetinib induced an ORR of 57% (95% CI, 46%-68%) in 87 patients with NSCLC who had received previous treatment with platinum-based chemotherapy; the complete response rate achieved with the agent was 5.7%. Additionally, the median DOR with the agent had not yet been reached (95% CI, 15.2 months–not reached). Of 27 patients who were treatment naïve, the ORR was reported to be even higher, at 70% (95% CI, 50%-86%) and the CR rate was 11%.
The recommended dose for the use of the agent in adults and pediatric patients aged 12 years or older is 400 mg to be administered orally, once daily, on an empty stomach, according to the FDA. No food should be consumed for at least 2 hours prior and at least 1 hour following the receipt of pralsetinib.