Pralsetinib, an highly selective RET inhibitor, has shown positive outcomes in the international phase I/II ARROW trial, recently published in Nature Medicine: pralsetinib induced robust, durable responses in patients with RET fusion-positive cancers regardless of tumor type.
The Food and Drug Administration approved pralsetinib as a treatment for RET fusion-positive non-small cell lung cancer in September 2020 and for advanced RET-altered thyroid cancers in December 2020; thus authors wanted to determine if the therapy provided benefit beyond non-small cell lung cancer and thyroid cancers, enrolling patients with tumors such as pancreatic cancer, cholangiocarcinoma, sarcoma and neuroendocrine tumors. The study enrolled 29 patients with 12 different cancer types; most patients had metastatic disease (87%) and received prior therapies for their cancer (87%). The study results showed an overall response rate of 57% and a disease control rate of 83%; three patients (13%) had a confirmed complete response and 10 (43%) had a confirmed partial response. The median duration of response was 11.7 months, the median progression-free survival was 7.4 months, and the median overall survival was 13.6 months. Treatment-related side effects were observed in 25 patients (86%), and 20 patients (69%) experienced grade 3 or higher adverse events. A total of 17 patients (59%) had short-term dose interruptions and 13 patients (45%) had permanent dose reductions due to side effects. «Although RET fusions are extremely rare beyond lung and thyroid cancers, these patients need effective therapies», said corresponding author Vivek Subbiah, from the University of Texas MD Anderson Cancer Center. «Overall, these data highlight the need for broad RET testing to identify candidates who may benefit from treatment with pralsetinib. Enrollment of patients with other RET fusion–positive solid tumors in ARROW is ongoing. These findings demonstrate the potential for RET inhibitors to benefit patients across tumor types and show the power of precision medicine to match patients to the right targeted therapy based on the unique features of their cancer».
