As reported in the Journal of Clinical Oncology by Besse et al, the final report from the phase I/II ARROW trial supports the efficacy of the RET inhibitor pralsetinib in patients with advanced RET fusion–positive non–small cell lung cancer (NSCLC). The initial reports from the trial supported U.S. Food and Drug Administration approval of pralsetinib for metastatic RET-altered NSCLC and RET fusion–positive thyroid cancers.
Study Details
In the international trial, 281 patients with RET-altered NSCLC were treated with pralsetinib at 400 mg once daily, including 116 treatment-naive patients and 141 patients who had received prior platinum-based chemotherapy. The measurable disease population consisted of 259 patients, including 106 treatment-naive patients and 130 prior platinum patients.
Key Findings
Final database lock was in May 2024, representing an additional 42 months of follow-up from time of initial reports.
In patients with measurable disease, objective response rates were 70% (95% confidence interval [CI] = 64%–76%) overall, 78% (95% CI = 69%–86%) among treatment-naive patients, and 63% (95% CI = 54%–71%) among prior platinum patients.
Median overall survival was 44.3 months (95% CI = 30.9–53.1 months) among all patients, 50.1 months (95% CI = 28.3 months to not reached) among treatment-naive patients, and 39.7 months (95% CI = 27.8–53.2 months) among prior platinum patients. Median progression-free survival was 13.1 months (95% CI = 11.4–16.8 months), 12.1 months (95% CI = 9.2–16.6 months), and 16.4 months (95% CI = 11.4–23.5 months).
Common grade ≥ 3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths were reported (due to pneumonia, interstitial lung disease, and rhabdomyolysis). The longer-term safety profile was consistent with prior reports from the trial.
The investigators concluded: “Pralsetinib produced robust, durable responses with manageable safety in treatment-naive and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up.”
Justin F. Gainor, MD, of the Department of Medicine, Center for Thoracic Cancers, Massachusetts General Hospital Cancer Center, Boston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Blueprint Medicines and Genentech/Roche. For full disclosures of the study authors, visit ascopubs.org.
