The following is the summary of “Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial” published in the November 2022 issue of Oncology by Griesinger, et al.

From 1% to 2% of NSCLC cases have RET fusions (NSCLC). Patients with RET fusion-positive NSCLC, including treatment-naive patients, responded favorably to dasatinib in phase I/II ARROW investigation, demonstrating clinical activity with this highly powerful, oral, central nervous system-penetrant, selective RET inhibitor. The latest ARROW research findings are reported. The ARROW study is a multi-cohort, open-label, phase I/II trial. Patients with locally advanced or metastatic solid tumors and an Eastern Cooperative Oncology Group performance status of 0-2 were considered for enrollment (later 0-1). Prior to illness progression, intolerance, withdrawal of consent, or investigator’s decision, patients started pralsetinib at the recommended phase II dose of 400 mg once a day. Phase II primary objectives included safety and overall response rate (ORR) as assessed by a central blinded review.

Researchers enrolled 281 people with RET fusion-positive NSCLC between March 17, 2017, and November 6, 2020 (when researchers stopped collecting data). Treatment-naive patients saw an ORR of 72% [54/75; 95% CI 60% to 82%], while those who had previously received platinum-based chemotherapy saw an ORR of 59% [80/136; 95% CI 50% to 67%) (enrollment cut-off for efficacy analysis: 22 May 2020); the median duration of response was not reached for treatment-naive patients but was 22.3 months for those who had previously received platinum-based chemotherapy. Median progression-free survival was 13.5 months for patients who had never received treatment and 16.5 months for those who had previously received platinum-based chemotherapy. The intracranial response rate was 70% (7/10; 95% CI 35% to 93%) in patients with detectable brain metastases who had previously undergone systemic treatment. Neutropenia (18%), hypertension (10%), elevated blood creatine phosphokinase (9%), and lymphopenia (9%) were the most prevalent treatment-related adverse events (TRAEs) among treatment-naive patients with RET fusion-positive NSCLC who initiated pralsetinib by the data cut-off (n=116). 

Twenty out of 281 patients dropped out because of TRAEs, or 7%. Patients with advanced RET fusion-positive NSCLC who had no prior treatment responded well to dasatinib and saw a high rate of clinical benefit. Precise data comparing pralsetinib to the current standard of therapy in the first-line context from the confirmatory phase III AcceleRET Lung study (NCT04222972) are still being analyzed.