On August 9, 2023, the FDA granted regular approval to pralsetinib (Gavreto; Genentech), a kinase inhibitor of wild-type RET and oncogenic RET fusions and mutations, for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) and RET fusion–positive gene mutation, as detected by an FDA-approved test.
Oral pralsetinib is also indicated for the treatment of patients aged ≥12 years with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate).
Pralsetinib was previously granted accelerated approval for the NSCLC indication on September 4, 2020, based on initial objective response rate (ORR) and duration of response (DOR) in 114 patients with NSCLC and RET fusion–positive disease who were enrolled in the ARROW study, a multicenter, open-label, multicohort clinical trial. During that accelerated approval, the FDA also approved the Oncomine Dx test as a companion diagnostic for pralsetinib.
The FDA’s conversion of the accelerated approval to regular approval for patients with NSCLC and RET fusion–positive disease was based on data from an additional 123 patients and 25 months of additional follow-up to assess durability of response to pralsetinib in patients. The patients received pralsetinib therapy until disease progression or unacceptable toxicity.
The primary efficacy measures in the ARROW study were ORR and DOR, as determined by a blinded independent review committee. Among 107 treatment-naïve patients, the ORR was 78% (95% confidence interval [CI], 68-85), with a median DOR of 13.4 months (95% CI, 9.4-23.1). Among 130 patients who had been previously treated with platinum-based chemotherapy, the ORR was 63% (95% CI, 54-71), with a median DOR of 38.8 months (95% CI, 14.8-not estimable).
The most common (≥25%) adverse reactions in the ARROW trial were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.
