Final ARROW Study Data Shows Pralsetinib Achieves 70% Response Rate in RET+ NSCLC with Durable Survival Outcomes
核心洞察
Rigel Pharmaceuticals published final Phase 1/2 ARROW study results in the Journal of Clinical Oncology, showing pralsetinib achieved a 70% overall response rate in patients with RET fusion-positive non-small cell lung cancer (搜索).
The study demonstrated median overall survival of 44.3 months in the overall population, with treatment-naïve patients achieving 50.1 months and prior-platinum patients reaching 39.7 months.
Pralsetinib showed intracranial activity with a 53% response rate in patients with measurable CNS metastases (搜索), supporting its potential value in advanced disease management.
Rigel Pharmaceuticals announced publication of final data from the Phase 1/2 ARROW study evaluating pralsetinib (GAVRETO®) for metastatic RET fusion-positive non-small cell lung cancer (搜索) (NSCLC (搜索)) in the Journal of Clinical Oncology. The final analysis includes an additional 42 months of follow-up from previously published data, demonstrating sustained efficacy and a manageable safety profile for the once-daily oral RET (搜索) inhibitor.
Robust Response Rates Across Patient Populations
Among 259 patients with measurable disease, pralsetinib achieved an overall response rate (ORR) of 70%, including 7% complete responses and 63% partial responses. Treatment-naïve patients demonstrated superior outcomes with a 78% ORR compared to 63% in patients who had received prior platinum-based chemotherapy.
"The final data from the ARROW study shows robust and durable responses with a manageable safety profile in patients with RET (搜索) fusion-positive NSCLC (搜索), emphasizing the importance of early biomarker testing and suggesting that pralsetinib may be a valuable tool in the treatment armamentarium," said Justin F. Gainor, M.D., Phase 1/2 trial investigator and Director of the Center for Thoracic Cancers at Mass General Brigham Cancer Institute (搜索).
Extended Survival Outcomes
The study revealed median overall survival (OS) of 44.3 months in the overall measurable disease population, with median follow-up of 47.6 months. Treatment-naïve patients achieved a median OS of 50.1 months (median follow-up 43.7 months), while patients with prior platinum therapy reached 39.7 months (median follow-up 49.7 months).
Geographic variations in survival outcomes were notable, with patients treated in the United States demonstrating longer median OS (62.4 months) compared to those in Asia (44.5 months) or Europe (29.6 months). Similarly, median progression-free survival was 13.1 months overall but extended to 25.9 months in U.S. patients versus 12.6 months in Asia and 12.8 months in Europe.
CNS Activity and Fusion Partner Analysis
Fifteen patients had measurable central nervous system metastases at baseline, with an intracranial response rate of 53%. Among 11 response-evaluable patients with CNS metastases (搜索), the CNS ORR reached 73%.
"The responses observed in the subset of patients with measurable CNS metastases (搜索) at baseline further expand the potential clinical value of pralsetinib in everyday practice," noted Dr. Gainor.
The analysis revealed differential responses based on RET (搜索) fusion partners. Patients with CCDC6 (搜索) fusions demonstrated longer median duration of response (47.9 months) compared to those with KIF5B (搜索) fusions (13.1 months), though ORR remained high in both subgroups across treatment-naïve and prior platinum-treated populations.
Safety Profile Remains Manageable
Pralsetinib maintained a manageable toxicity profile consistent with previous reports. Three treatment-related deaths occurred in treatment-naïve patients in Asia (pneumonia in two patients; interstitial lung disease and rhabdomyolysis in one patient each). No new safety signals emerged, and no hypersensitivity reactions were reported in patients receiving prior immunotherapies.
The median treatment duration was 15.0 months at final data lock. Common adverse reactions included musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough.
Clinical Context and Implications
RET (搜索) fusions occur in approximately 1-2% of NSCLC (搜索) patients, representing a small but clinically significant population. With over 229,000 adults expected to be diagnosed with lung cancer (搜索) in the U.S. in 2026, and NSCLC accounting for 77% of all lung cancer diagnoses, targeted therapies like pralsetinib address critical unmet needs in precision oncology.
"These longer-term data further support pralsetinib's role as a first-line treatment option for RET (搜索) fusion-positive NSCLC (搜索) patients," said Lisa Rojkjaer, M.D., Rigel's chief medical officer.
Pralsetinib is currently indicated for adult patients with metastatic RET (搜索) fusion-positive NSCLC (搜索) as detected by an FDA-approved test, as well as for adult and pediatric patients 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer (搜索) requiring systemic therapy.