Lei Wang ¹ Yafei You ² Wenzhuo He ³ Yu Hou ¹ Lan Li ¹ Wang Li ¹ Chang Jiang ³ Jiahong Yi ³ Yaoxiong Xia ¹ Liangping Xia ^3*

• ¹ Yunnan Cancer Hospital, Kunming, China
• ² Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China
• ³ Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong Province, China

Background: Pralsetinib is a selective RET inhibitor. The ARROW trial revealed that RET fusion-positive non-small-cell lung cancer (NSCLC) can benefit from pralsetinib with tolerable adverse events (AEs). However, the efficacy and safety of pralsetinib in real world has rarely been reported. Materials and Methods: This study reviewed the efficacy and safety of pralsetinib in RET fusion-positive NSCLC patients between March 2021 and December 2021. Progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and log-rank test. A Cox regression model was performed to identify independent prognostic factors. Results: A total of 28 patients were enrolled, and the median follow-up time was 18.1 months. The objective response rate and disease control rate of the whole cohort were 57.2% and 71.4%, respectively, and the median PFS and OS were 8.1 months (95% confidence interval [CI], 3.1-13.2) and 13.8 months (95% CI, 2.8-24.8), respectively. Baseline characteristics of the treatment naive group and pre-treated group were listed. The median PFS tended to be better in treatment naive group (18.3 vs. 8.0 months, P=0.067), while the median OS were similar between the two groups (28.4 vs. 11.6 months, P=0.308). Patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2 had worse median PFS comparing with those with ECOG PS score of 0-1 (3.8 vs. 12.6 months, P=0.004). Besides, patients previously treated with platinum-based chemotherapy (PBC) also revealed worse median PFS (8.0 vs. 18.6 months, P=0.023) comparing with those without previous PBC. Furthermore, patients previously treated with anti-programmed death-1 (PD-1) antibody or multikinase inhibitors (MKIs) showed worse median OS compared with those without previous anti-PD-1 antibody (5.0 vs. 22.0 months, P=0.002) or MKIs (6.2 vs. 28.4 months, P=0.015). The most common AEs was increased aspartate aminotransferase (39.3%). Conclusion: Pralsetinib was effective in RET fusion-positive NSCLC with tolerable AEs in real-world practice. Efficacy of pralsetinib was decreased in patients previously treated with PBC, immunotherapy, or MKIs.