KEY TAKEAWAYS
- The updated results from the ARROW Phase 1 and 2 study in Chinese patients with advanced RET fusion+ NSCLC demonstrate a deep and durable response and long-term clinical benefit with pralsetinib.
- The ORR was 66.7% in previously treated patients and 83.3% in treatment-naïve patients, with a manageable safety profile and no new safety signals detected.
- Median PFS was 11.7 months in previously treated patients and 12.7 months in treatment-naïve patients, with 24-month and 18-month PFS rates of 37.5% and 36.2%, respectively.
- Pralsetinib shows a favorable benefit-risk profile and offers a transformative medicine to Chinese RET-fusion-driven advanced NSCLC patients.
To date, pralsetinib is the only RET inhibitor to receive Chinese regulatory approval. ARROW is a worldwide phase I/II registrational trial testing the effectiveness and safety of pralsetinib in patients with advanced solid cancers who have RET alterations (NSCLC). They report revised findings from the ARROW research conducted on Chinese patients with RET fusion+ NSCLC of advanced stage. Transcriptional Elongation Factor Fusion Plus Patients with Chinese NSCLC were enrolled and given pralsetinib 400 mg QD, regardless of whether or not they had previously received platinum-based chemotherapy. The primary objectives were a measure of safety and an objective response rate (ORR) based on a central, blinded review using RECIST v1.1 criteria.
About 68 Chinese patients with RET fusion+ NSCLC had been treated with pralsetinib as of March 4, 2022. The overall response rate (ORR) in 33 patients with measurable lesions at baseline among the 37 patients who had received prior platinum-based chemotherapy was 66.7% (22/33; 95% CI 48-82; 1 CR, 21 PR), and the median progression-free survival (PFS) (95% CI) was 11.7 months (8.7; -). The 24-month PFS rate was 37.5%. The overall response rate (ORR) was 83.3% (25/30, 95% CI 65-94; 2 CR, 23 PR) in treatment-naive patients with detectable lesions at baseline, and the median progression-free survival (PFS) (95% CI) was 12.7 months (8.9; -). The 18-month PFS rate was 36.2%. Aspartate aminotransferase elevation (82%) was the most common treatment-related adverse event (TRAE) reported by all patients with NSCLC (N=68), followed by neutrophil count reduction (79%), anemia (72%), white blood cell count reduction (62%), and alanine aminotransferase elevation (57%). About 11.8% of those using pralsetinib stopped taking it because of adverse events.
Chinese individuals with RET fusion+ NSCLC who have undergone or have not undergone prior platinum-based chemotherapy continue to show deep and persistent response and long-term therapeutic benefits with pralsetinib, even after prolonged periods of follow-up. The latest findings from the ARROW experiment align with those previously reported. In addition, Pralsetinib’s adverse effects in Chinese patients are controllable, and no new safety signals have been identified. Overall, the benefit-risk profile of pralsetinib was positive, making it a potentially game-changing medication for Chinese patients with RET-fusion-driven advanced NSCLC.
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03037385
Z. Qing, Y. Wu, J. Zhao, J. Chang, H. Wang, Y. Fan, K. Wang, G. Wu, W. Nian, Y. Gong, Y. Sun, M. Sun, X. Wang, H. Shi, X. Zheng, M. Qin, X. Duan, Z. Shen, S. Yao, J. Yang. (2022). 389P – Updated efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion+ non-small cell lung cancer. Annals of Oncology (2022) 33 (suppl_9): S1560-S1597. 10.1016/annonc/annonc1134.
