Long-term follow-up of the oral selective RET inhibitor pralsetinib in patients with advanced non–small cell lung cancer (NSCLC) and a RET fusion confirms its efficacy and safety, according to final findings from the phase I/II ARROW trial published in the Journal of Clinical Oncology.
“Before selective RET inhibitors were developed, the expected overall survival for advanced RET fusion–positive NSCLC was roughly between 4 and 11 months. Now we show that pralsetinib can extend the median survival rate to 44 months,” said senior author Justin Gainor, MD, Division Chief, Solid Tumor Medical Oncology at Mass General Brigham Cancer Institute. “Our findings reinforce the importance of early biomarker testing, including testing for gene fusions, in all patients [with metastatic NSCLC] to guide treatment.”
Background and Study Methods
RET fusions occur in about 1% to 2% of all cases of NSCLC.
The open-label, multicenter phase I/II ARROW trial explored the use of pralsetinib in patients with thyroid cancer, NSCLC, and other advanced solid tumors. Prior findings from the ARROW study led to the U.S. Food and Drug Administration (FDA) approval of pralsetinib for the treatment of patients with RET fusion–positive NSCLC as well as for patients with RET-altered thyroid cancers.
Final findings from the NSCLC cohort treated with 400 mg of the agent in the ARROW study were released, accounting for an additional 42 months of follow-up.
Key Findings
At the data lock of May 20, 2024, patients (n = 281) had a median treatment duration of 15 months.
The overall response rate (n = 259 evaluable patients) was 78% (95% confidence interval [CI] = 69%–86%) in treatment-naive patients and 63% (95% CI = 54%–71%) in patients who had previously received platinum-based chemotherapy.
The median overall survival was 44.3 months (95% CI = 30.9–53.1 months) overall, 50.1 months for treatment-naive patients (95% CI = 28.3 months to not reached), and 39.7 months for patients with prior platinum chemotherapy exposure (95% CI = 27.8–53.2 months).
In treatment-naive patients with CCDC6 or KIF5B fusion partners, response rates were higher, at 84% and 79%, respectively; patients with CCFC6-RET fusions also had a significantly longer duration of response compared with patients with KIF5B-RET fusions (47.9 vs 13.1 months).
The most common treatment-related adverse events of grade 3 or higher were anemia in 21% of patients, hypertension in 15%, and decreased neutrophil counts in 13%. Treatment-related deaths occurred in three patients; two had pneumonia, and one patient each had interstitial lung disease and rhabdomyolysis.
No hypersensitivity was observed in patients who had previously received immunotherapy.
"Pralsetinib produced robust, durable responses with manageable safety in treatment-naive and previously treated patients with RET fusion–positive NSCLC, confirming previous findings with longer follow-up," the study authors concluded.
DISCLOSURES: The study was supported by Blueprint Medicines and Genentech/Roche. Dr. Wekken and Dr. Thomassen are employees of Rigel Pharmaceuticals, Inc. For full disclosures of the other study authors, visit ascopubs.org.
