Background The incidence of RET gene fusion translocation in non-small cell lung cancer (NSCLC) patients in China ranges from 1.4% to 2.5%, and pralsetinib is the first high-selective RET inhibitor approved for marketing in China, with significant efficacy. However, its application still lacks real-world data validation.

Objective To investigate the real-world effectiveness and safety profile of pralsetinib, a specific inhibitor, in the management of non-small cell lung cancer (NSCLC) with RET gene alterations.

Methods Clinical data from 39 patients with locally advanced or metastatic NSCLC who tested positive for RET fusion and received pralsetinib treatment in Chinese PLA General Hospital from March 2017 to October 2022 were retrospectively analyzed. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and drug safety evaluations for first-line, second-line, and subsequent pralsetinib treatments were analyzed.

Results Among the 39 enrolled patients, there were 24 female patients (61.5%) with a median age of 59 (range: 34-81) years. First-line treatment was administered to 26 cases (66.7%), while second-line or subsequent treatments were given to 13 cases (33.3%). At treatment initiation, intracranial metastases were found in 13 patients (33.3%). In patients receiving pralsetinib as first-line therapy, the DCR was 88.5%, the ORR was 50.0%, and both median TTF and PFS were recorded as 11.7 months. For those undergoing second-line or later treatments, the DCR was 76.9%, ORR was 23.1%, with median TTF of 8.2 months and median PFS of 9.0 months. Among the 13 patients with intracranial metastases, the DCR was 84.6%, while the ORR reached 46.2%. Treatment-related adverse reactions were observed in 32 cases (82.1%), with decreased hemoglobin levels being the most prevalent side effect (13 cases; 33.3%). Other adverse reactions included reduced neutrophil count in 12 cases (30.8%), elevated AST levels in 11 cases (28.2%), increased blood pressure in 10 cases (25.6%), raised ALT levels in 10 cases (25%), and diminished lymphocyte count in 9 cases (23%). Notably, 5 patients experienced grade 3/4 infectious pneumonia, but no treatment-related deaths occurred.

Conclusion Pralsetinib has demonstrated robust clinical efficacy and sustained response in the treatment of locally advanced or metastatic RET fusion-positive NSCLC. Notably, it exhibits notable control over intracranial lesions and maintains excellent safety profile. However, vigilance is required for the identification of pralsetinib-associated pneumonia.